Development of micro- and nanosystems as carriers for drugs with anti-inflammatory effect and methods for their characterization

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Development of micro- and nanosystems as carriers for drugs with anti-inflammatory effect and methods for their characterization (en)
Развој микро- и наносистема као носача за лекове са антиинфламаторним деловањем и метода за њихову карактеризацију (sr)
Razvoj mikro- i nanosistema kao nosača za lekove sa antiinflamatornim delovanjem i metoda za njihovu karakterizaciju (sr_RS)
Authors

Publications

Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance

Savić, Vedrana

(Универзитет у Београду, Фармацеутски факултет, 2021)

TY  - THES
AU  - Savić, Vedrana
PY  - 2021
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=8413
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:24645/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48734473
UR  - https://nardus.mpn.gov.rs/handle/123456789/18775
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4034
AB  - dermatitisa. Danas je na tržištu registrovan samo jedan farmaceutski oblik sa takrolimusom zaprimenu na koži - mast. Zbog nepoželjnih karakteristika masti (masna tekstura, teško razmazivanje,sporo upijanje, teško spiranje) i težnje da se poboljša njegova isporuka u kožu, sve je veća potrebaza razvojem novih, naprednih nosača sa takrolimusom, kao što su mikroemulzije, nanoemulzije ilipidne nanočestice.Usled njihove kompleksnosti, razvoj ovih nosača je dugotrajan i neizvestan proces. Stoga jecilj ove doktorske disertacije bio formulisanje mikroemulzija, nanoemulzija i nanostrukturiranihlipidnih čestica stabilizovanih lecitinom, kao nosača za dermalnu isporuku takrolimusa.Perspektivni nosači su podvrgnuti sveobuhvatnoj fizičkohemijskoj karakterizaciji i studijistabilnosti, a dermalna isporuka takrolimusa upoređena je sa referentnom mašću.Formulaciona istraživanja omogućila su skupljanje znanja o kritičnim formulacionim iprocesnim parametarima za dobijanje stabilnih nosača sa takrolimusom. U dvočasovnoj in vitrostudiji penetracije takrolimusa u kožu uha svinje korišćenjem metode sa trakama, uočeno je da surazvijeni nosači superiorniji u poređenju sa referentnom mašću i omogućavaju bolju isporukutakrolimusa u stratum corneum. Takrolimus je u značajnoj meri penetrirao u folikule dlaka, štododatno može da osigura bolju dermalnu isporuku. Ipak, rezultati 24-časovne in vitro studijepermeacije kroz kožu uha svinje pune debljine korišćenjem Franz-ovih difuzionih ćelija ukazuju nabolju permeaciju takrolimusa iz mikroemulzije i referentne masti u poređenju sa nanostrukturiranimlipidnim česticama i nanoemulzijom, što može ukazivati i na mogućnost ispoljavanja sistemskihneželjenih efekata.Generalno, rezultati ukazuju na veliki potencijal dobijenih nosača za dermalnu isporukutakrolimusa, što bi trebalo potvrditi odgovarajućim kliničkim eksperimentalnim postavkama.
AB  - Tacrolimus is a potent immunosuppressive macrolide which is topically used for treatment ofatopic dermatitis. Today, there is only one pharmaceutical form for topical application of tacrolimus- tacrolimus ointment. Due to the undesirable characteristics of ointments (greasy texture, difficultyof applying and spreading onto the skin, difficulty to wash them off) and desirable enhancement indermal delivery, there is an emerging need for development of novel carriers for tacrolimus, such asmicroemulsions, nanoemulsions and lipid nanoparticles.Owing to their complexity, the development of these carriers can be a long-lasting anduncertain process. Therefore, the aim of this doctoral thesis was to formulate lecithin basedmicroemulsions, nanoemulsions and nanostructured lipid carriers as novel carriers for dermaldelivery of tacrolimus. The physicochemical characteristics and stability of promising carriers wasassessed, and dermal delivery of tacrolimus was compared to the referent ointment.The formulation evaluation acquired important knowledge about the critical parameters forobtaining stabile carriers with tacrolimus. Results of in vitro penetration of tacrolimus in porcine earskin suggested superiority of the developed carriers compared to the referent ointment.Additionally, the delivery of tacrolimus into the hair follicles was increased as well, which couldprovide better dermal delivery of tacrolimus. On the other hand, the results of 24-hour in vitropermeation study using Franz diffusion cells and full thickness porcine ear skin indicated betterpermeation of tacrolimus from the microemulsion and the referent ointment compared to thenanostructured lipid carrier and the nanoemulsion, which can also suggest a risk of systemicadverse effects by their usage.Overall, the developed carriers could be suggested as promising carriers for dermal deliveryof tacrolimus, which should be confirmed by appropriate clinical evaluation.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18775
ER  - 
@phdthesis{
author = "Savić, Vedrana",
year = "2021",
abstract = "dermatitisa. Danas je na tržištu registrovan samo jedan farmaceutski oblik sa takrolimusom zaprimenu na koži - mast. Zbog nepoželjnih karakteristika masti (masna tekstura, teško razmazivanje,sporo upijanje, teško spiranje) i težnje da se poboljša njegova isporuka u kožu, sve je veća potrebaza razvojem novih, naprednih nosača sa takrolimusom, kao što su mikroemulzije, nanoemulzije ilipidne nanočestice.Usled njihove kompleksnosti, razvoj ovih nosača je dugotrajan i neizvestan proces. Stoga jecilj ove doktorske disertacije bio formulisanje mikroemulzija, nanoemulzija i nanostrukturiranihlipidnih čestica stabilizovanih lecitinom, kao nosača za dermalnu isporuku takrolimusa.Perspektivni nosači su podvrgnuti sveobuhvatnoj fizičkohemijskoj karakterizaciji i studijistabilnosti, a dermalna isporuka takrolimusa upoređena je sa referentnom mašću.Formulaciona istraživanja omogućila su skupljanje znanja o kritičnim formulacionim iprocesnim parametarima za dobijanje stabilnih nosača sa takrolimusom. U dvočasovnoj in vitrostudiji penetracije takrolimusa u kožu uha svinje korišćenjem metode sa trakama, uočeno je da surazvijeni nosači superiorniji u poređenju sa referentnom mašću i omogućavaju bolju isporukutakrolimusa u stratum corneum. Takrolimus je u značajnoj meri penetrirao u folikule dlaka, štododatno može da osigura bolju dermalnu isporuku. Ipak, rezultati 24-časovne in vitro studijepermeacije kroz kožu uha svinje pune debljine korišćenjem Franz-ovih difuzionih ćelija ukazuju nabolju permeaciju takrolimusa iz mikroemulzije i referentne masti u poređenju sa nanostrukturiranimlipidnim česticama i nanoemulzijom, što može ukazivati i na mogućnost ispoljavanja sistemskihneželjenih efekata.Generalno, rezultati ukazuju na veliki potencijal dobijenih nosača za dermalnu isporukutakrolimusa, što bi trebalo potvrditi odgovarajućim kliničkim eksperimentalnim postavkama., Tacrolimus is a potent immunosuppressive macrolide which is topically used for treatment ofatopic dermatitis. Today, there is only one pharmaceutical form for topical application of tacrolimus- tacrolimus ointment. Due to the undesirable characteristics of ointments (greasy texture, difficultyof applying and spreading onto the skin, difficulty to wash them off) and desirable enhancement indermal delivery, there is an emerging need for development of novel carriers for tacrolimus, such asmicroemulsions, nanoemulsions and lipid nanoparticles.Owing to their complexity, the development of these carriers can be a long-lasting anduncertain process. Therefore, the aim of this doctoral thesis was to formulate lecithin basedmicroemulsions, nanoemulsions and nanostructured lipid carriers as novel carriers for dermaldelivery of tacrolimus. The physicochemical characteristics and stability of promising carriers wasassessed, and dermal delivery of tacrolimus was compared to the referent ointment.The formulation evaluation acquired important knowledge about the critical parameters forobtaining stabile carriers with tacrolimus. Results of in vitro penetration of tacrolimus in porcine earskin suggested superiority of the developed carriers compared to the referent ointment.Additionally, the delivery of tacrolimus into the hair follicles was increased as well, which couldprovide better dermal delivery of tacrolimus. On the other hand, the results of 24-hour in vitropermeation study using Franz diffusion cells and full thickness porcine ear skin indicated betterpermeation of tacrolimus from the microemulsion and the referent ointment compared to thenanostructured lipid carrier and the nanoemulsion, which can also suggest a risk of systemicadverse effects by their usage.Overall, the developed carriers could be suggested as promising carriers for dermal deliveryof tacrolimus, which should be confirmed by appropriate clinical evaluation.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18775"
}
Savić, V.. (2021). Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_18775
Savić V. Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance. in Универзитет у Београду. 2021;.
https://hdl.handle.net/21.15107/rcub_nardus_18775 .
Savić, Vedrana, "Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance" in Универзитет у Београду (2021),
https://hdl.handle.net/21.15107/rcub_nardus_18775 .

Permeability and biocompatibility evaluation of olopatadine hydrochloride viscous ophthalmic solutions using in vitro 3D corneal model

Račić, Anđelka; Jurišić Dukovski, Bisera; Lovrić, Jasmina; Dobričić, Vladimir; Čalija, Bojan; Milić, Jela; Krajišnik, Danina

(International Association for Pharmaceutical Technology, Mainz, Germany, 2021)

TY  - CONF
AU  - Račić, Anđelka
AU  - Jurišić Dukovski, Bisera
AU  - Lovrić, Jasmina
AU  - Dobričić, Vladimir
AU  - Čalija, Bojan
AU  - Milić, Jela
AU  - Krajišnik, Danina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5481
AB  - Olopatadine is a selective H1-receptore antagonist that
inhibits release of histamine and proinflammatory
mediators [1]. The poor ocular bioavailability, as the main
limitation of efficient ocular therapy, could be overcome by
increasing residence time and enhancing corneal
penetration. ...
PB  - International Association for Pharmaceutical Technology, Mainz, Germany
C3  - 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
T1  - Permeability and biocompatibility evaluation of olopatadine hydrochloride viscous ophthalmic solutions using in vitro 3D corneal model
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5481
ER  - 
@conference{
author = "Račić, Anđelka and Jurišić Dukovski, Bisera and Lovrić, Jasmina and Dobričić, Vladimir and Čalija, Bojan and Milić, Jela and Krajišnik, Danina",
year = "2021",
abstract = "Olopatadine is a selective H1-receptore antagonist that
inhibits release of histamine and proinflammatory
mediators [1]. The poor ocular bioavailability, as the main
limitation of efficient ocular therapy, could be overcome by
increasing residence time and enhancing corneal
penetration. ...",
publisher = "International Association for Pharmaceutical Technology, Mainz, Germany",
journal = "12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting",
title = "Permeability and biocompatibility evaluation of olopatadine hydrochloride viscous ophthalmic solutions using in vitro 3D corneal model",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5481"
}
Račić, A., Jurišić Dukovski, B., Lovrić, J., Dobričić, V., Čalija, B., Milić, J.,& Krajišnik, D.. (2021). Permeability and biocompatibility evaluation of olopatadine hydrochloride viscous ophthalmic solutions using in vitro 3D corneal model. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
International Association for Pharmaceutical Technology, Mainz, Germany..
https://hdl.handle.net/21.15107/rcub_farfar_5481
Račić A, Jurišić Dukovski B, Lovrić J, Dobričić V, Čalija B, Milić J, Krajišnik D. Permeability and biocompatibility evaluation of olopatadine hydrochloride viscous ophthalmic solutions using in vitro 3D corneal model. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_5481 .
Račić, Anđelka, Jurišić Dukovski, Bisera, Lovrić, Jasmina, Dobričić, Vladimir, Čalija, Bojan, Milić, Jela, Krajišnik, Danina, "Permeability and biocompatibility evaluation of olopatadine hydrochloride viscous ophthalmic solutions using in vitro 3D corneal model" in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting (2021),
https://hdl.handle.net/21.15107/rcub_farfar_5481 .

Polyglycerol ester-based low energy nanoemulsions with red raspberry seed oil and fruit extracts: Formulation development toward effective in vitro/in vivo bioperformance

Gledović, Ana; Janošević-Ležaić, Aleksandra; Nikolić, Ines; Tasić-Kostov, Marija; Antić-Stanković, Jelena; Krstonošić, Veljko; Ranđelović, Danijela; Božić, Dragana; Ilić, Dušan; Tamburić, Slobodanka; Savić, Snežana

(MDPI AG, 2021)

TY  - JOUR
AU  - Gledović, Ana
AU  - Janošević-Ležaić, Aleksandra
AU  - Nikolić, Ines
AU  - Tasić-Kostov, Marija
AU  - Antić-Stanković, Jelena
AU  - Krstonošić, Veljko
AU  - Ranđelović, Danijela
AU  - Božić, Dragana
AU  - Ilić, Dušan
AU  - Tamburić, Slobodanka
AU  - Savić, Snežana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3777
AB  - This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions were obtained via phase inversion composition (PIC) method at room temperature by dilution of microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic, rheological and Differential Scanning Calorimetry (DSC) investigations. The results have shown that the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet size (Z-ave: 50 to 70 nm, PDI value ≤ 0.1). The highest antioxidant activity (~92% inhibition of the DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles and significant improvement in skin hydration during 2 h after application for all nanoemulsions. Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin protection and hydration.
PB  - MDPI AG
T2  - Nanomaterials
T1  - Polyglycerol ester-based low energy nanoemulsions with red raspberry seed oil and fruit extracts: Formulation development toward effective in vitro/in vivo bioperformance
VL  - 11
IS  - 1
SP  - 1
EP  - 21
DO  - 10.3390/nano11010217
ER  - 
@article{
author = "Gledović, Ana and Janošević-Ležaić, Aleksandra and Nikolić, Ines and Tasić-Kostov, Marija and Antić-Stanković, Jelena and Krstonošić, Veljko and Ranđelović, Danijela and Božić, Dragana and Ilić, Dušan and Tamburić, Slobodanka and Savić, Snežana",
year = "2021",
abstract = "This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions were obtained via phase inversion composition (PIC) method at room temperature by dilution of microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic, rheological and Differential Scanning Calorimetry (DSC) investigations. The results have shown that the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet size (Z-ave: 50 to 70 nm, PDI value ≤ 0.1). The highest antioxidant activity (~92% inhibition of the DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles and significant improvement in skin hydration during 2 h after application for all nanoemulsions. Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin protection and hydration.",
publisher = "MDPI AG",
journal = "Nanomaterials",
title = "Polyglycerol ester-based low energy nanoemulsions with red raspberry seed oil and fruit extracts: Formulation development toward effective in vitro/in vivo bioperformance",
volume = "11",
number = "1",
pages = "1-21",
doi = "10.3390/nano11010217"
}
Gledović, A., Janošević-Ležaić, A., Nikolić, I., Tasić-Kostov, M., Antić-Stanković, J., Krstonošić, V., Ranđelović, D., Božić, D., Ilić, D., Tamburić, S.,& Savić, S.. (2021). Polyglycerol ester-based low energy nanoemulsions with red raspberry seed oil and fruit extracts: Formulation development toward effective in vitro/in vivo bioperformance. in Nanomaterials
MDPI AG., 11(1), 1-21.
https://doi.org/10.3390/nano11010217
Gledović A, Janošević-Ležaić A, Nikolić I, Tasić-Kostov M, Antić-Stanković J, Krstonošić V, Ranđelović D, Božić D, Ilić D, Tamburić S, Savić S. Polyglycerol ester-based low energy nanoemulsions with red raspberry seed oil and fruit extracts: Formulation development toward effective in vitro/in vivo bioperformance. in Nanomaterials. 2021;11(1):1-21.
doi:10.3390/nano11010217 .
Gledović, Ana, Janošević-Ležaić, Aleksandra, Nikolić, Ines, Tasić-Kostov, Marija, Antić-Stanković, Jelena, Krstonošić, Veljko, Ranđelović, Danijela, Božić, Dragana, Ilić, Dušan, Tamburić, Slobodanka, Savić, Snežana, "Polyglycerol ester-based low energy nanoemulsions with red raspberry seed oil and fruit extracts: Formulation development toward effective in vitro/in vivo bioperformance" in Nanomaterials, 11, no. 1 (2021):1-21,
https://doi.org/10.3390/nano11010217 . .
3
14
3
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Nanosuspensions of novel deuterated pyrazoloquinolinones ligand (DK-I-56-1): lyophilization procedure development through cryoprotectant selection and stability study

Mitrović, Jelena; Bjelošević, Maja; Đoković, Jelena; Ahlin Grabnar, Pegi; Planinšek, Odon; Knutson, Daniel; Cook, James; Savić, Miroslav; Savić, Snežana

(2020)

TY  - CONF
AU  - Mitrović, Jelena
AU  - Bjelošević, Maja
AU  - Đoković, Jelena
AU  - Ahlin Grabnar, Pegi
AU  - Planinšek, Odon
AU  - Knutson, Daniel
AU  - Cook, James
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3744
AB  - Despite of good pharmacodynamics of DK-I-56-1, novel deuterated pyrazoloquinolinones ligand, low solubility limits its administration. Nanosuspensions can help to overcome this problem, but its small particle size usually leads to particle agglomeration in short period of time. This phenomenon can be prevented by performing lyophilization. In this study cryoprotectants selection as well as characterization (particle size measurements after redispersion, scanning electron microscopy, differential scanning calorimetry and thermogravimetric measurements) of obtained freeze dried preparations was carried out. It was observed that sucrose/mannitol ratio 1:1 and 3:2 in total concentration of 10% can preserve particle size during lyophilization. However, after stability study conducted during one month storage at 25 °C and 40 °C, particle size remained in submicron range only in one sample. Changes in particle size were also followed by changes in polymorphic form of mannitol. It can be concluded that changes of crystal forms in freeze dried preparations during storage could jeopardize their stability, and therefore should be carefully examined.
T1  - Nanosuspensions of novel deuterated pyrazoloquinolinones ligand (DK-I-56-1): lyophilization procedure development through cryoprotectant selection and stability study
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3744
ER  - 
@conference{
author = "Mitrović, Jelena and Bjelošević, Maja and Đoković, Jelena and Ahlin Grabnar, Pegi and Planinšek, Odon and Knutson, Daniel and Cook, James and Savić, Miroslav and Savić, Snežana",
year = "2020",
abstract = "Despite of good pharmacodynamics of DK-I-56-1, novel deuterated pyrazoloquinolinones ligand, low solubility limits its administration. Nanosuspensions can help to overcome this problem, but its small particle size usually leads to particle agglomeration in short period of time. This phenomenon can be prevented by performing lyophilization. In this study cryoprotectants selection as well as characterization (particle size measurements after redispersion, scanning electron microscopy, differential scanning calorimetry and thermogravimetric measurements) of obtained freeze dried preparations was carried out. It was observed that sucrose/mannitol ratio 1:1 and 3:2 in total concentration of 10% can preserve particle size during lyophilization. However, after stability study conducted during one month storage at 25 °C and 40 °C, particle size remained in submicron range only in one sample. Changes in particle size were also followed by changes in polymorphic form of mannitol. It can be concluded that changes of crystal forms in freeze dried preparations during storage could jeopardize their stability, and therefore should be carefully examined.",
title = "Nanosuspensions of novel deuterated pyrazoloquinolinones ligand (DK-I-56-1): lyophilization procedure development through cryoprotectant selection and stability study",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3744"
}
Mitrović, J., Bjelošević, M., Đoković, J., Ahlin Grabnar, P., Planinšek, O., Knutson, D., Cook, J., Savić, M.,& Savić, S.. (2020). Nanosuspensions of novel deuterated pyrazoloquinolinones ligand (DK-I-56-1): lyophilization procedure development through cryoprotectant selection and stability study. .
https://hdl.handle.net/21.15107/rcub_farfar_3744
Mitrović J, Bjelošević M, Đoković J, Ahlin Grabnar P, Planinšek O, Knutson D, Cook J, Savić M, Savić S. Nanosuspensions of novel deuterated pyrazoloquinolinones ligand (DK-I-56-1): lyophilization procedure development through cryoprotectant selection and stability study. 2020;.
https://hdl.handle.net/21.15107/rcub_farfar_3744 .
Mitrović, Jelena, Bjelošević, Maja, Đoković, Jelena, Ahlin Grabnar, Pegi, Planinšek, Odon, Knutson, Daniel, Cook, James, Savić, Miroslav, Savić, Snežana, "Nanosuspensions of novel deuterated pyrazoloquinolinones ligand (DK-I-56-1): lyophilization procedure development through cryoprotectant selection and stability study" (2020),
https://hdl.handle.net/21.15107/rcub_farfar_3744 .

Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance

Mitrović, Jelena; Divović, Branka; Knutson, Daniel E.; Đoković, Jelena; Vulić, Predrag; Ranđelović, Danijela; Dobričić, Vladimir; Čalija, Bojan; Cook, James M.; Savić, Miroslav; Savić, Snežana

(Elsevier B.V., 2020)

TY  - JOUR
AU  - Mitrović, Jelena
AU  - Divović, Branka
AU  - Knutson, Daniel E.
AU  - Đoković, Jelena
AU  - Vulić, Predrag
AU  - Ranđelović, Danijela
AU  - Dobričić, Vladimir
AU  - Čalija, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3640
AB  - DK-I-56–1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders. During preclinical investigation of poorly water-soluble compounds such as DK-I-56–1, the application of nanotechnology could be advantageous due to improved safety and possibly increased bioavailability of nanosized formulation. DK-I-56–1 nanosuspensions stabilized by polysorbate 80, alone or in combination with poloxamers 188 i.e. 407 or d-α-tocopheryl polyethylene glycol 1000 succinate, were prepared using a small-scale media milling device. With particle size 208.7–250.6 nm and polydispersity index <0.250, selected nanodiseprsions were stable for three weeks. Pharmacokinetic and biodistribution studies following intraperitoneal administration of three types of formulation in mice indicated high plasma DK-I-56–1 levels after solution (10,228.6 ± 1037.2 ngh/ml) and nanosuspension (6770.4 ± 770.7 ngh/ml) but not suspension administration (966.0 ± 58.1 ngh/ml). However, distribution of DK-I-56–1 after solution was heavily influenced by its composition, and brain availability of nanosuspension was superior to that of solution formulation. In spontaneous locomotor activity test, the expected hyperlocomotor effect was observed after nanosuspension administration, without compromising impact of the vehicle/excipients used. Therefore, nanonization of drug compound assembled with proper selection of stabilizers may seemingly contribute further thorough testing of DK-I-56–1 preclinical efficacy.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance
VL  - 152
DO  - 10.1016/j.ejps.2020.105432
ER  - 
@article{
author = "Mitrović, Jelena and Divović, Branka and Knutson, Daniel E. and Đoković, Jelena and Vulić, Predrag and Ranđelović, Danijela and Dobričić, Vladimir and Čalija, Bojan and Cook, James M. and Savić, Miroslav and Savić, Snežana",
year = "2020",
abstract = "DK-I-56–1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders. During preclinical investigation of poorly water-soluble compounds such as DK-I-56–1, the application of nanotechnology could be advantageous due to improved safety and possibly increased bioavailability of nanosized formulation. DK-I-56–1 nanosuspensions stabilized by polysorbate 80, alone or in combination with poloxamers 188 i.e. 407 or d-α-tocopheryl polyethylene glycol 1000 succinate, were prepared using a small-scale media milling device. With particle size 208.7–250.6 nm and polydispersity index <0.250, selected nanodiseprsions were stable for three weeks. Pharmacokinetic and biodistribution studies following intraperitoneal administration of three types of formulation in mice indicated high plasma DK-I-56–1 levels after solution (10,228.6 ± 1037.2 ngh/ml) and nanosuspension (6770.4 ± 770.7 ngh/ml) but not suspension administration (966.0 ± 58.1 ngh/ml). However, distribution of DK-I-56–1 after solution was heavily influenced by its composition, and brain availability of nanosuspension was superior to that of solution formulation. In spontaneous locomotor activity test, the expected hyperlocomotor effect was observed after nanosuspension administration, without compromising impact of the vehicle/excipients used. Therefore, nanonization of drug compound assembled with proper selection of stabilizers may seemingly contribute further thorough testing of DK-I-56–1 preclinical efficacy.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance",
volume = "152",
doi = "10.1016/j.ejps.2020.105432"
}
Mitrović, J., Divović, B., Knutson, D. E., Đoković, J., Vulić, P., Ranđelović, D., Dobričić, V., Čalija, B., Cook, J. M., Savić, M.,& Savić, S.. (2020). Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 152.
https://doi.org/10.1016/j.ejps.2020.105432
Mitrović J, Divović B, Knutson DE, Đoković J, Vulić P, Ranđelović D, Dobričić V, Čalija B, Cook JM, Savić M, Savić S. Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance. in European Journal of Pharmaceutical Sciences. 2020;152.
doi:10.1016/j.ejps.2020.105432 .
Mitrović, Jelena, Divović, Branka, Knutson, Daniel E., Đoković, Jelena, Vulić, Predrag, Ranđelović, Danijela, Dobričić, Vladimir, Čalija, Bojan, Cook, James M., Savić, Miroslav, Savić, Snežana, "Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance" in European Journal of Pharmaceutical Sciences, 152 (2020),
https://doi.org/10.1016/j.ejps.2020.105432 . .
7
3
7

Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala

Bubić Pajić, Nataša

(Универзитет у Београду, Фармацеутски факултет, 2020)

TY  - THES
AU  - Bubić Pajić, Nataša
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7642
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:22707/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=18378761
UR  - https://nardus.mpn.gov.rs/handle/123456789/17504
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3719
AB  - Primarni cilj istraživanja ove doktorske disertacije je bila procena mogućnosti da se razvojemi primenom mikroemulzija (kao opcije hemijskog inhensera penetracije) poboljša dermalnaisporuka slabo rastvorljivih lekovitih supstanci – adapalena (ADA) i sertakonazol-nitrata (SN), kojepripadaju različitim farmakoterapijskim grupama, imaju različite fizičkohemijske osobine iprimenjuju se u različitim terapijskim koncentracijama. Mikroemulzije su stabilizovane nejonskimsurfaktantima novije generacije – alkil poligukozidima (APG) ili polioksietilen(glicerol) estrimamasnih kiselina. U cilju komparativne procene doprinosa različitih vrsta nosača dermalnojraspoloživosti model leka, posebna pažnja je posvećena analizi sposobnosti različitih vrstamikroigala (fizički inhenseri penetracije) da pojačaju isporuku SN u kožu (čvrste silikonske vs.rastvorljive mikroigle).Rezultati su ukazali da se još uvek nedovoljno korišćeni APG surfaktanti i gliceret-7-kaprilat/kaprat mogu uspešno primeniti u formulaciji mikroemulzija. Razvijene (invertne)bikontinuirane mikroemulzije su se pokazale kao pogodni nosači za solubilizovanje ADA i SN, upogledu njihovih fizičkohemijskih osobina, bezbednosti i stabilnosti, i, najvažnije, u pogledunjihovog potencijala za poboljšanje dermalne isporuke ovih lekova in vitro. Dodatno, rastvorljivemikroigle su uspešno formulisane kao nosači za dermalnu isporuku teško rastvorljivog SN iobezbedile komparabilno deponovanje leka u koži kao mikroemulzije, međutim uz prisustvo invitro transdermalne isporuke dela primenjene doze leka. Sinergističko delovanje mikroigala imikroemulzija bilo je superiorno u odnosu primenu samog fizičkog i samog hemijskogpremošćivača barijere stratum corneum-a, bez značajnog povećanja permeacije leka.
AB  - The aim of this doctoral dissertation was to evaluate the possibility of using microemulsions(as chemical penetration inerters) for improvment of dermal delivery of a poorly soluble modeldugs having different physicochemical characteristics, belonging to different pharmacotherapeuticgroups, i.e. applied in different therapeutic concentrations (adapalene (ADA) and sertaconazolenitrate (SN)). Microemulsions were stabilized with newer nonionic surfactants - alkylpolygucosides (APG) or polyoxyethylene (glycerol) fatty acid esters. In order to compare thecontribution of different types of carriers to the enhancement of dermal availability of the modeldrug, a special attention has been paid to the assessment of microneedles ability to significantlyimprove delivery of SN into the skin (dissolvable vs. solid silicone microneedles).The obtained results showed that newer and so far insufficiently used APG surfactants andglycereth-7-caprylate/caprate can be successfully applied in the formulation of microemulsions. Thedeveloped (invert) bicontinuous microemulsion formulations have proved to be suitable carriers forsolubilizing the investigated model drugs, in terms of their physicochemical properties, safetyprofile and stability, and, most importantly, their great potential of improving dermal delivery ofADA and SN in vitro. In addition, dissolvable microneedles were successfully fabricated as carriersfor dermal delivery o highly lipophilic SN and provided comparable drug deposition in the skin asmicroemulsions, but coupled with transdermal delivery of a portion of the administered drug dose.The synergistic action of microneedles and microemulsions was superior over the application eitherof physical or chemical enhancer alone, without reaching a significant increase in drug permeationas compared to the use of dissolvable microneedles.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala
UR  - https://hdl.handle.net/21.15107/rcub_nardus_17504
ER  - 
@phdthesis{
author = "Bubić Pajić, Nataša",
year = "2020",
abstract = "Primarni cilj istraživanja ove doktorske disertacije je bila procena mogućnosti da se razvojemi primenom mikroemulzija (kao opcije hemijskog inhensera penetracije) poboljša dermalnaisporuka slabo rastvorljivih lekovitih supstanci – adapalena (ADA) i sertakonazol-nitrata (SN), kojepripadaju različitim farmakoterapijskim grupama, imaju različite fizičkohemijske osobine iprimenjuju se u različitim terapijskim koncentracijama. Mikroemulzije su stabilizovane nejonskimsurfaktantima novije generacije – alkil poligukozidima (APG) ili polioksietilen(glicerol) estrimamasnih kiselina. U cilju komparativne procene doprinosa različitih vrsta nosača dermalnojraspoloživosti model leka, posebna pažnja je posvećena analizi sposobnosti različitih vrstamikroigala (fizički inhenseri penetracije) da pojačaju isporuku SN u kožu (čvrste silikonske vs.rastvorljive mikroigle).Rezultati su ukazali da se još uvek nedovoljno korišćeni APG surfaktanti i gliceret-7-kaprilat/kaprat mogu uspešno primeniti u formulaciji mikroemulzija. Razvijene (invertne)bikontinuirane mikroemulzije su se pokazale kao pogodni nosači za solubilizovanje ADA i SN, upogledu njihovih fizičkohemijskih osobina, bezbednosti i stabilnosti, i, najvažnije, u pogledunjihovog potencijala za poboljšanje dermalne isporuke ovih lekova in vitro. Dodatno, rastvorljivemikroigle su uspešno formulisane kao nosači za dermalnu isporuku teško rastvorljivog SN iobezbedile komparabilno deponovanje leka u koži kao mikroemulzije, međutim uz prisustvo invitro transdermalne isporuke dela primenjene doze leka. Sinergističko delovanje mikroigala imikroemulzija bilo je superiorno u odnosu primenu samog fizičkog i samog hemijskogpremošćivača barijere stratum corneum-a, bez značajnog povećanja permeacije leka., The aim of this doctoral dissertation was to evaluate the possibility of using microemulsions(as chemical penetration inerters) for improvment of dermal delivery of a poorly soluble modeldugs having different physicochemical characteristics, belonging to different pharmacotherapeuticgroups, i.e. applied in different therapeutic concentrations (adapalene (ADA) and sertaconazolenitrate (SN)). Microemulsions were stabilized with newer nonionic surfactants - alkylpolygucosides (APG) or polyoxyethylene (glycerol) fatty acid esters. In order to compare thecontribution of different types of carriers to the enhancement of dermal availability of the modeldrug, a special attention has been paid to the assessment of microneedles ability to significantlyimprove delivery of SN into the skin (dissolvable vs. solid silicone microneedles).The obtained results showed that newer and so far insufficiently used APG surfactants andglycereth-7-caprylate/caprate can be successfully applied in the formulation of microemulsions. Thedeveloped (invert) bicontinuous microemulsion formulations have proved to be suitable carriers forsolubilizing the investigated model drugs, in terms of their physicochemical properties, safetyprofile and stability, and, most importantly, their great potential of improving dermal delivery ofADA and SN in vitro. In addition, dissolvable microneedles were successfully fabricated as carriersfor dermal delivery o highly lipophilic SN and provided comparable drug deposition in the skin asmicroemulsions, but coupled with transdermal delivery of a portion of the administered drug dose.The synergistic action of microneedles and microemulsions was superior over the application eitherof physical or chemical enhancer alone, without reaching a significant increase in drug permeationas compared to the use of dissolvable microneedles.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala",
url = "https://hdl.handle.net/21.15107/rcub_nardus_17504"
}
Bubić Pajić, N.. (2020). Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_17504
Bubić Pajić N. Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala. in Универзитет у Београду. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_17504 .
Bubić Pajić, Nataša, "Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala" in Универзитет у Београду (2020),
https://hdl.handle.net/21.15107/rcub_nardus_17504 .

Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass

Čalija, Bojan; Milić, Jela; Milašinović, Nikola; Daković, Aleksandra; Trifković, Kata; Stojanović, Jovica

(Wiley Periodicals, Inc., 2020)

TY  - JOUR
AU  - Čalija, Bojan
AU  - Milić, Jela
AU  - Milašinović, Nikola
AU  - Daković, Aleksandra
AU  - Trifković, Kata
AU  - Stojanović, Jovica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3478
AB  - This study was designed to investigate functionality of tetracycline‐loaded chitosan‐halloysite nanocomposite films, with focus on evaluating the influence of chitosan molar mass on films applicability for sustained local antibiotic delivery. The films were prepared by casting and solvent evaporation using low, medium, and high molar mass chitosan. SEM analysis revealed compact, nonporous and rough surface of the nanocomposite films due to the presence of halloysite agglomerates and tetracycline crystals. Increasing chitosan molar mass led to higher values of elongation at break (from 21.65 ± 2.65 to 34.48 ± 2.34%), tensile strength (from 134.8 ± 13.21 to 246.36 ± 14.69 MPa), and elastic modulus (from 633.79 ± 128.37 to 716.55 ± 60.76 MPa) of the nanocomposite films. FT‐IR, XRPD, and thermal analyses confirmed molar mass dependent chitosan‐halloysite interactions and improved thermal stability of the nanocomposite films in comparison with chitosan films. The nanocomposite films released tetracycline in a sustained manner, with the slowest release achieved from the films consisting of low molar mass chitosan. Chitosan molar mass was confirmed to be a functionality‐related characteristic of chitosan‐halloysite nanocomposite films as potential sustained‐release carriers for topical delivery of antibiotics
PB  - Wiley Periodicals, Inc.
T2  - Journal of Applied Polymer Science
T1  - Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass
VL  - 137
IS  - 8
DO  - 10.1002/app.48406
ER  - 
@article{
author = "Čalija, Bojan and Milić, Jela and Milašinović, Nikola and Daković, Aleksandra and Trifković, Kata and Stojanović, Jovica",
year = "2020",
abstract = "This study was designed to investigate functionality of tetracycline‐loaded chitosan‐halloysite nanocomposite films, with focus on evaluating the influence of chitosan molar mass on films applicability for sustained local antibiotic delivery. The films were prepared by casting and solvent evaporation using low, medium, and high molar mass chitosan. SEM analysis revealed compact, nonporous and rough surface of the nanocomposite films due to the presence of halloysite agglomerates and tetracycline crystals. Increasing chitosan molar mass led to higher values of elongation at break (from 21.65 ± 2.65 to 34.48 ± 2.34%), tensile strength (from 134.8 ± 13.21 to 246.36 ± 14.69 MPa), and elastic modulus (from 633.79 ± 128.37 to 716.55 ± 60.76 MPa) of the nanocomposite films. FT‐IR, XRPD, and thermal analyses confirmed molar mass dependent chitosan‐halloysite interactions and improved thermal stability of the nanocomposite films in comparison with chitosan films. The nanocomposite films released tetracycline in a sustained manner, with the slowest release achieved from the films consisting of low molar mass chitosan. Chitosan molar mass was confirmed to be a functionality‐related characteristic of chitosan‐halloysite nanocomposite films as potential sustained‐release carriers for topical delivery of antibiotics",
publisher = "Wiley Periodicals, Inc.",
journal = "Journal of Applied Polymer Science",
title = "Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass",
volume = "137",
number = "8",
doi = "10.1002/app.48406"
}
Čalija, B., Milić, J., Milašinović, N., Daković, A., Trifković, K.,& Stojanović, J.. (2020). Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass. in Journal of Applied Polymer Science
Wiley Periodicals, Inc.., 137(8).
https://doi.org/10.1002/app.48406
Čalija B, Milić J, Milašinović N, Daković A, Trifković K, Stojanović J. Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass. in Journal of Applied Polymer Science. 2020;137(8).
doi:10.1002/app.48406 .
Čalija, Bojan, Milić, Jela, Milašinović, Nikola, Daković, Aleksandra, Trifković, Kata, Stojanović, Jovica, "Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass" in Journal of Applied Polymer Science, 137, no. 8 (2020),
https://doi.org/10.1002/app.48406 . .
8
3
7

Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity

Gledović, Ana; Janošević-Ležaić, Aleksandra; Krstonošić, Veljko; Đoković, Jelena; Nikolić, Ines; Bajuk-Bogdanović, Danica; Antić-Stanković, Jelena; Ranđelović, Danijela; Savić, Sanela M.; Filipović, Mila; Tamburić, Slobodanka; Savić, Snežana

(Public Library of Science, 2020)

TY  - JOUR
AU  - Gledović, Ana
AU  - Janošević-Ležaić, Aleksandra
AU  - Krstonošić, Veljko
AU  - Đoković, Jelena
AU  - Nikolić, Ines
AU  - Bajuk-Bogdanović, Danica
AU  - Antić-Stanković, Jelena
AU  - Ranđelović, Danijela
AU  - Savić, Sanela M.
AU  - Filipović, Mila
AU  - Tamburić, Slobodanka
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3581
AB  - Considering a growing demand for medicinal/cosmetic products with natural actives, this study focuses on the low-energy nanoemulsions (LE-NEs) prepared via the Phase inversion composition (PIC) method at room temperature as potential carriers for natural oil. Four different red raspberry seed oils (ROs) were tested, as follows: cold-pressed vs. CO2- extracted, organic vs. non-organic, refined vs. unrefined. The oil phase was optimized with Tocopheryl acetate and Isostearyl isostearate, while water phase was adjusted with either glycerol or an antioxidant hydro-glycolic extract. This study has used a combined approach to formulation development, employing both conventional methods (pseudo-ternary phase diagram - PTPD, electrical conductivity, particle size measurements, microscopical analysis, and rheological measurements) and the methods novel to this area, such as textural analysis and Raman spectroscopy. Raman spectroscopy has detected fine differences in chemical composition among ROs, and it detected the interactions within nanoemulsions. It was shown that the cold-pressed, unrefined, organic grade oil (RO2) with 6.62% saturated fatty acids and 92.25% unsaturated fatty acids, was optimal for the LE-NEs. Textural analysis confirmed the existence of cubic gel-like phase as a crucial step in the formation of stable RO2-loaded LE-NEs, with droplets in the narrow nano-range (125 to 135 nm; PDI ≤ 0.1). The DPPH test in methanol and ABTS in aqueous medium have revealed a synergistic free radical scavenging effect between lipophilic and hydrophilic antioxidants in LE-NEs. The nanoemulsion carrier has improved the biological effect of raw materials on HeLa cervical adenocarcinoma cells, while exhibiting good safety profile, as confirmed on MRC-5 normal human lung fibroblasts. Overall, this study has shown that low-energy nanoemulsions present very promising carriers for topical delivery of natural bioactives. Raman spectroscopy and textural analysis have proven to be a useful addition to the arsenal of methods used in the formulation and characterization of nanoemulsion systems.
PB  - Public Library of Science
T2  - PLoS ONE
T1  - Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity
VL  - 15
IS  - 4
DO  - 10.1371/journal.pone.0230993
ER  - 
@article{
author = "Gledović, Ana and Janošević-Ležaić, Aleksandra and Krstonošić, Veljko and Đoković, Jelena and Nikolić, Ines and Bajuk-Bogdanović, Danica and Antić-Stanković, Jelena and Ranđelović, Danijela and Savić, Sanela M. and Filipović, Mila and Tamburić, Slobodanka and Savić, Snežana",
year = "2020",
abstract = "Considering a growing demand for medicinal/cosmetic products with natural actives, this study focuses on the low-energy nanoemulsions (LE-NEs) prepared via the Phase inversion composition (PIC) method at room temperature as potential carriers for natural oil. Four different red raspberry seed oils (ROs) were tested, as follows: cold-pressed vs. CO2- extracted, organic vs. non-organic, refined vs. unrefined. The oil phase was optimized with Tocopheryl acetate and Isostearyl isostearate, while water phase was adjusted with either glycerol or an antioxidant hydro-glycolic extract. This study has used a combined approach to formulation development, employing both conventional methods (pseudo-ternary phase diagram - PTPD, electrical conductivity, particle size measurements, microscopical analysis, and rheological measurements) and the methods novel to this area, such as textural analysis and Raman spectroscopy. Raman spectroscopy has detected fine differences in chemical composition among ROs, and it detected the interactions within nanoemulsions. It was shown that the cold-pressed, unrefined, organic grade oil (RO2) with 6.62% saturated fatty acids and 92.25% unsaturated fatty acids, was optimal for the LE-NEs. Textural analysis confirmed the existence of cubic gel-like phase as a crucial step in the formation of stable RO2-loaded LE-NEs, with droplets in the narrow nano-range (125 to 135 nm; PDI ≤ 0.1). The DPPH test in methanol and ABTS in aqueous medium have revealed a synergistic free radical scavenging effect between lipophilic and hydrophilic antioxidants in LE-NEs. The nanoemulsion carrier has improved the biological effect of raw materials on HeLa cervical adenocarcinoma cells, while exhibiting good safety profile, as confirmed on MRC-5 normal human lung fibroblasts. Overall, this study has shown that low-energy nanoemulsions present very promising carriers for topical delivery of natural bioactives. Raman spectroscopy and textural analysis have proven to be a useful addition to the arsenal of methods used in the formulation and characterization of nanoemulsion systems.",
publisher = "Public Library of Science",
journal = "PLoS ONE",
title = "Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity",
volume = "15",
number = "4",
doi = "10.1371/journal.pone.0230993"
}
Gledović, A., Janošević-Ležaić, A., Krstonošić, V., Đoković, J., Nikolić, I., Bajuk-Bogdanović, D., Antić-Stanković, J., Ranđelović, D., Savić, S. M., Filipović, M., Tamburić, S.,& Savić, S.. (2020). Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity. in PLoS ONE
Public Library of Science., 15(4).
https://doi.org/10.1371/journal.pone.0230993
Gledović A, Janošević-Ležaić A, Krstonošić V, Đoković J, Nikolić I, Bajuk-Bogdanović D, Antić-Stanković J, Ranđelović D, Savić SM, Filipović M, Tamburić S, Savić S. Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity. in PLoS ONE. 2020;15(4).
doi:10.1371/journal.pone.0230993 .
Gledović, Ana, Janošević-Ležaić, Aleksandra, Krstonošić, Veljko, Đoković, Jelena, Nikolić, Ines, Bajuk-Bogdanović, Danica, Antić-Stanković, Jelena, Ranđelović, Danijela, Savić, Sanela M., Filipović, Mila, Tamburić, Slobodanka, Savić, Snežana, "Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity" in PLoS ONE, 15, no. 4 (2020),
https://doi.org/10.1371/journal.pone.0230993 . .
1
21
6
20

Curcumin-loaded low-energy nanoemulsions: Linking EPR spectroscopy-analysed microstructure and antioxidant potential with in vitro evaluated biological activity

Nikolić, Ines; Mitsou, Evgenia; Damjanović, Ana; Papadimitriou, Vassiliki; Antić-Stanković, Jelena; Stanojević, Boban; Xenakis, Aristotelis; Savić, Snežana

(Elsevier B.V., 2020)

TY  - JOUR
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Damjanović, Ana
AU  - Papadimitriou, Vassiliki
AU  - Antić-Stanković, Jelena
AU  - Stanojević, Boban
AU  - Xenakis, Aristotelis
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3528
AB  - The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI < 0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.
PB  - Elsevier B.V.
T2  - Journal of Molecular Liquids
T1  - Curcumin-loaded low-energy nanoemulsions: Linking EPR spectroscopy-analysed microstructure and antioxidant potential with in vitro evaluated biological activity
VL  - 301
DO  - 10.1016/j.molliq.2020.112479
ER  - 
@article{
author = "Nikolić, Ines and Mitsou, Evgenia and Damjanović, Ana and Papadimitriou, Vassiliki and Antić-Stanković, Jelena and Stanojević, Boban and Xenakis, Aristotelis and Savić, Snežana",
year = "2020",
abstract = "The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI < 0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.",
publisher = "Elsevier B.V.",
journal = "Journal of Molecular Liquids",
title = "Curcumin-loaded low-energy nanoemulsions: Linking EPR spectroscopy-analysed microstructure and antioxidant potential with in vitro evaluated biological activity",
volume = "301",
doi = "10.1016/j.molliq.2020.112479"
}
Nikolić, I., Mitsou, E., Damjanović, A., Papadimitriou, V., Antić-Stanković, J., Stanojević, B., Xenakis, A.,& Savić, S.. (2020). Curcumin-loaded low-energy nanoemulsions: Linking EPR spectroscopy-analysed microstructure and antioxidant potential with in vitro evaluated biological activity. in Journal of Molecular Liquids
Elsevier B.V.., 301.
https://doi.org/10.1016/j.molliq.2020.112479
Nikolić I, Mitsou E, Damjanović A, Papadimitriou V, Antić-Stanković J, Stanojević B, Xenakis A, Savić S. Curcumin-loaded low-energy nanoemulsions: Linking EPR spectroscopy-analysed microstructure and antioxidant potential with in vitro evaluated biological activity. in Journal of Molecular Liquids. 2020;301.
doi:10.1016/j.molliq.2020.112479 .
Nikolić, Ines, Mitsou, Evgenia, Damjanović, Ana, Papadimitriou, Vassiliki, Antić-Stanković, Jelena, Stanojević, Boban, Xenakis, Aristotelis, Savić, Snežana, "Curcumin-loaded low-energy nanoemulsions: Linking EPR spectroscopy-analysed microstructure and antioxidant potential with in vitro evaluated biological activity" in Journal of Molecular Liquids, 301 (2020),
https://doi.org/10.1016/j.molliq.2020.112479 . .
20
19

Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?

Nikolić, Ines; Mitsou, Evgenia; Pantelić, Ivana; Ranđelović, Danijela; Marković, Bojan; Papadimitriou, Vassiliki; Xenakis, Aristotelis; Lunter, Dominique Jasmin; Žugić, Ana; Savić, Snežana

(Elsevier B.V., 2020)

TY  - JOUR
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Pantelić, Ivana
AU  - Ranđelović, Danijela
AU  - Marković, Bojan
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Lunter, Dominique Jasmin
AU  - Žugić, Ana
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3507
AB  - The objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers. Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml. Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?
VL  - 142
DO  - 10.1016/j.ejps.2019.105135
ER  - 
@article{
author = "Nikolić, Ines and Mitsou, Evgenia and Pantelić, Ivana and Ranđelović, Danijela and Marković, Bojan and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Lunter, Dominique Jasmin and Žugić, Ana and Savić, Snežana",
year = "2020",
abstract = "The objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers. Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml. Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?",
volume = "142",
doi = "10.1016/j.ejps.2019.105135"
}
Nikolić, I., Mitsou, E., Pantelić, I., Ranđelović, D., Marković, B., Papadimitriou, V., Xenakis, A., Lunter, D. J., Žugić, A.,& Savić, S.. (2020). Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 142.
https://doi.org/10.1016/j.ejps.2019.105135
Nikolić I, Mitsou E, Pantelić I, Ranđelović D, Marković B, Papadimitriou V, Xenakis A, Lunter DJ, Žugić A, Savić S. Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?. in European Journal of Pharmaceutical Sciences. 2020;142.
doi:10.1016/j.ejps.2019.105135 .
Nikolić, Ines, Mitsou, Evgenia, Pantelić, Ivana, Ranđelović, Danijela, Marković, Bojan, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Lunter, Dominique Jasmin, Žugić, Ana, Savić, Snežana, "Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?" in European Journal of Pharmaceutical Sciences, 142 (2020),
https://doi.org/10.1016/j.ejps.2019.105135 . .
1
31
18
28

Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application

Pantelić, Ivana; Lukić, Milica; Gojgić-Cvijović, Gordana; Jakovljević, Dragica; Nikolić, Ines; Lunter, Dominique Jasmin; Daniels, Rolf; Savić, Snežana

(Elsevier, 2020)

TY  - JOUR
AU  - Pantelić, Ivana
AU  - Lukić, Milica
AU  - Gojgić-Cvijović, Gordana
AU  - Jakovljević, Dragica
AU  - Nikolić, Ines
AU  - Lunter, Dominique Jasmin
AU  - Daniels, Rolf
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3500
AB  - Ongoing demand in sustainable and biocompatible drug dosage forms is reflected in the search for novel pharmaceutical excipients with equal properties. A group of microbial exopolysaccharides offers a variety of biopolymers with many alleged uses and effects. This study aims to assess applicative properties of levan obtained from Bacillus licheniformis NS032, focusing on its potential co-stabilizing and drug release-controlling functions in pertaining emulsion systems. Despite its high molecular weight and partial existence in globular nanometric structures (180-190 nm), levan was successfully incorporated into both tested colloidal systems: those stabilized with synthetic/anionic or natural-origin/non-ionic emulsifiers. In the tested levan concentrations range (0.2-3.0% w/w) the monitored flow and thermal parameters failed to show linear concentration dependence, which prompted us to revisit certain colloidal fundamentals of this biopolymer. Being a part of the external phase of the investigated emulsion systems, levan contributed to formation of a matrix-like environment, offering additional stabilization of the microstructure and rheology modifying properties (hysteresis loop elevation as high as 4167±98 to 20792±3166 Pa•s−1), especially in case of the samples where lamellar liquid crystalline formation occurred. Apart from its good water solubility and considerable conformational flexibility, the investigated homofructan easily saturated the external phase of the samples stabilized with a conventional anionic emulsifier, leading to similar properties of 0.2% and 3.0% levan-containing samples. After closer consideration of thermal and release behavior, this was considered as a favorable property for a novel excipient, offering tailored formulation characteristics even with lower levan concentrations, consequently not compromising the potential cost of the final drug dosage form.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application
VL  - 142
DO  - 10.1016/j.ejps.2019.105109
ER  - 
@article{
author = "Pantelić, Ivana and Lukić, Milica and Gojgić-Cvijović, Gordana and Jakovljević, Dragica and Nikolić, Ines and Lunter, Dominique Jasmin and Daniels, Rolf and Savić, Snežana",
year = "2020",
abstract = "Ongoing demand in sustainable and biocompatible drug dosage forms is reflected in the search for novel pharmaceutical excipients with equal properties. A group of microbial exopolysaccharides offers a variety of biopolymers with many alleged uses and effects. This study aims to assess applicative properties of levan obtained from Bacillus licheniformis NS032, focusing on its potential co-stabilizing and drug release-controlling functions in pertaining emulsion systems. Despite its high molecular weight and partial existence in globular nanometric structures (180-190 nm), levan was successfully incorporated into both tested colloidal systems: those stabilized with synthetic/anionic or natural-origin/non-ionic emulsifiers. In the tested levan concentrations range (0.2-3.0% w/w) the monitored flow and thermal parameters failed to show linear concentration dependence, which prompted us to revisit certain colloidal fundamentals of this biopolymer. Being a part of the external phase of the investigated emulsion systems, levan contributed to formation of a matrix-like environment, offering additional stabilization of the microstructure and rheology modifying properties (hysteresis loop elevation as high as 4167±98 to 20792±3166 Pa•s−1), especially in case of the samples where lamellar liquid crystalline formation occurred. Apart from its good water solubility and considerable conformational flexibility, the investigated homofructan easily saturated the external phase of the samples stabilized with a conventional anionic emulsifier, leading to similar properties of 0.2% and 3.0% levan-containing samples. After closer consideration of thermal and release behavior, this was considered as a favorable property for a novel excipient, offering tailored formulation characteristics even with lower levan concentrations, consequently not compromising the potential cost of the final drug dosage form.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application",
volume = "142",
doi = "10.1016/j.ejps.2019.105109"
}
Pantelić, I., Lukić, M., Gojgić-Cvijović, G., Jakovljević, D., Nikolić, I., Lunter, D. J., Daniels, R.,& Savić, S.. (2020). Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application. in European Journal of Pharmaceutical Sciences
Elsevier., 142.
https://doi.org/10.1016/j.ejps.2019.105109
Pantelić I, Lukić M, Gojgić-Cvijović G, Jakovljević D, Nikolić I, Lunter DJ, Daniels R, Savić S. Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application. in European Journal of Pharmaceutical Sciences. 2020;142.
doi:10.1016/j.ejps.2019.105109 .
Pantelić, Ivana, Lukić, Milica, Gojgić-Cvijović, Gordana, Jakovljević, Dragica, Nikolić, Ines, Lunter, Dominique Jasmin, Daniels, Rolf, Savić, Snežana, "Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application" in European Journal of Pharmaceutical Sciences, 142 (2020),
https://doi.org/10.1016/j.ejps.2019.105109 . .
24
6
23

Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass

Čalija, Bojan; Milić, Jela; Milašinović, Nikola; Daković, Aleksandra; Trifković, Kata; Stojanović, Jovica; Krajišnik, Danina

(Wiley Periodicals, Inc., 2020)

TY  - JOUR
AU  - Čalija, Bojan
AU  - Milić, Jela
AU  - Milašinović, Nikola
AU  - Daković, Aleksandra
AU  - Trifković, Kata
AU  - Stojanović, Jovica
AU  - Krajišnik, Danina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3476
AB  - This study was designed to investigate functionality of tetracycline‐loaded chitosan‐halloysite nanocomposite films, with focus on evaluating the influence of chitosan molar mass on films applicability for sustained local antibiotic delivery. The films were prepared by casting and solvent evaporation using low, medium, and high molar mass chitosan. SEM analysis revealed compact, nonporous and rough surface of the nanocomposite films due to the presence of halloysite agglomerates and tetracycline crystals. Increasing chitosan molar mass led to higher values of elongation at break (from 21.65 ± 2.65 to 34.48 ± 2.34%), tensile strength (from 134.8 ± 13.21 to 246.36 ± 14.69 MPa), and elastic modulus (from 633.79 ± 128.37 to 716.55 ± 60.76 MPa) of the nanocomposite films. FT‐IR, XRPD, and thermal analyses confirmed molar mass dependent chitosan‐halloysite interactions and improved thermal stability of the nanocomposite films in comparison with chitosan films. The nanocomposite films released tetracycline in a sustained manner, with the slowest release achieved from the films consisting of low molar mass chitosan. Chitosan molar mass was confirmed to be a functionality‐related characteristic of chitosan‐halloysite nanocomposite films as potential sustained‐release carriers for topical delivery of antibiotics.
PB  - Wiley Periodicals, Inc.
T2  - Journal of Applied Polymer Science
T1  - Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass
VL  - 137
IS  - 8
DO  - 10.1002/app.48406
ER  - 
@article{
author = "Čalija, Bojan and Milić, Jela and Milašinović, Nikola and Daković, Aleksandra and Trifković, Kata and Stojanović, Jovica and Krajišnik, Danina",
year = "2020",
abstract = "This study was designed to investigate functionality of tetracycline‐loaded chitosan‐halloysite nanocomposite films, with focus on evaluating the influence of chitosan molar mass on films applicability for sustained local antibiotic delivery. The films were prepared by casting and solvent evaporation using low, medium, and high molar mass chitosan. SEM analysis revealed compact, nonporous and rough surface of the nanocomposite films due to the presence of halloysite agglomerates and tetracycline crystals. Increasing chitosan molar mass led to higher values of elongation at break (from 21.65 ± 2.65 to 34.48 ± 2.34%), tensile strength (from 134.8 ± 13.21 to 246.36 ± 14.69 MPa), and elastic modulus (from 633.79 ± 128.37 to 716.55 ± 60.76 MPa) of the nanocomposite films. FT‐IR, XRPD, and thermal analyses confirmed molar mass dependent chitosan‐halloysite interactions and improved thermal stability of the nanocomposite films in comparison with chitosan films. The nanocomposite films released tetracycline in a sustained manner, with the slowest release achieved from the films consisting of low molar mass chitosan. Chitosan molar mass was confirmed to be a functionality‐related characteristic of chitosan‐halloysite nanocomposite films as potential sustained‐release carriers for topical delivery of antibiotics.",
publisher = "Wiley Periodicals, Inc.",
journal = "Journal of Applied Polymer Science",
title = "Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass",
volume = "137",
number = "8",
doi = "10.1002/app.48406"
}
Čalija, B., Milić, J., Milašinović, N., Daković, A., Trifković, K., Stojanović, J.,& Krajišnik, D.. (2020). Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass. in Journal of Applied Polymer Science
Wiley Periodicals, Inc.., 137(8).
https://doi.org/10.1002/app.48406
Čalija B, Milić J, Milašinović N, Daković A, Trifković K, Stojanović J, Krajišnik D. Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass. in Journal of Applied Polymer Science. 2020;137(8).
doi:10.1002/app.48406 .
Čalija, Bojan, Milić, Jela, Milašinović, Nikola, Daković, Aleksandra, Trifković, Kata, Stojanović, Jovica, Krajišnik, Danina, "Functionality of chitosan‐halloysite nanocomposite films for sustained delivery of antibiotics: The effect of chitosan molar mass" in Journal of Applied Polymer Science, 137, no. 8 (2020),
https://doi.org/10.1002/app.48406 . .
8
3
7

A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?

Lukić, Milica; Pantelić, Ivana; Savić, Snežana

(Blackwell Publishing Inc, 2020)

TY  - JOUR
AU  - Lukić, Milica
AU  - Pantelić, Ivana
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3725
AB  - Emollients are acknowledged as a part of standard care in therapeutic and prevention protocols as well as a part of everyday skin care routine. When it comes to making a final decision between two emollient products, the ingredient list, that is, the formulation composition could be the determining factor. In such cases the consumer, and some healthcare providers, believe that products with the same qualitative composition (ingredient list) must have the same efficacy. In this study, we have investigated the skin hydration performance of two emollient preparations (DBG and MBG), which appear to contain the same ingredients, and hence, could be considered interchangeable in everyday practice. Our studies showed that the effects of DBG were overall superior to the ones attributed to MBG at each investigated time point (1, 2, 4, and 24 h post application) when tested on normal and dry skin. Consequently, it is shown that two apparently qualitatively identical products do not necessarily provide matching efficacy.
PB  - Blackwell Publishing Inc
T2  - Dermatologic Therapy
T1  - A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?
VL  - 33
IS  - 6
DO  - 10.1111/dth.14020
ER  - 
@article{
author = "Lukić, Milica and Pantelić, Ivana and Savić, Snežana",
year = "2020",
abstract = "Emollients are acknowledged as a part of standard care in therapeutic and prevention protocols as well as a part of everyday skin care routine. When it comes to making a final decision between two emollient products, the ingredient list, that is, the formulation composition could be the determining factor. In such cases the consumer, and some healthcare providers, believe that products with the same qualitative composition (ingredient list) must have the same efficacy. In this study, we have investigated the skin hydration performance of two emollient preparations (DBG and MBG), which appear to contain the same ingredients, and hence, could be considered interchangeable in everyday practice. Our studies showed that the effects of DBG were overall superior to the ones attributed to MBG at each investigated time point (1, 2, 4, and 24 h post application) when tested on normal and dry skin. Consequently, it is shown that two apparently qualitatively identical products do not necessarily provide matching efficacy.",
publisher = "Blackwell Publishing Inc",
journal = "Dermatologic Therapy",
title = "A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?",
volume = "33",
number = "6",
doi = "10.1111/dth.14020"
}
Lukić, M., Pantelić, I.,& Savić, S.. (2020). A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?. in Dermatologic Therapy
Blackwell Publishing Inc., 33(6).
https://doi.org/10.1111/dth.14020
Lukić M, Pantelić I, Savić S. A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?. in Dermatologic Therapy. 2020;33(6).
doi:10.1111/dth.14020 .
Lukić, Milica, Pantelić, Ivana, Savić, Snežana, "A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?" in Dermatologic Therapy, 33, no. 6 (2020),
https://doi.org/10.1111/dth.14020 . .
3
2
3

Mikro- i nanostrukturirani emulzioni sistemi na bazi polihidroksilnih surfaktanata za isporuku aceklofenaka u/kroz kožu primenom hemijskih pojačivača penetracije i mikroigala

Ilić, Tanja

(Универзитет у Београду, Фармацеутски факултет, 2019)

TY  - THES
AU  - Ilić, Tanja
PY  - 2019
UR  - http://nardus.mpn.gov.rs/handle/123456789/12186
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7330
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:21377/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048435298
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3685
AB  - Imajući na umu ograničenu biološku raspoloţivost i posledično terapijski efekat nesteroidnih antiinflamatornih lekova (NSAIL) primenjenih na koţi, cilj doktorske disertacije bio je razvoj, optimizacija i sveobuhvatna fizičko-hemijska i biofarmaceutska karakterizacija ulje-u-vodi nanoemulzija, kao i konvencionalnih (mikrostrukturiranih) emulzionih sistema (podloga) na bazi prirodnih polihidroksilnih surfaktanata (saharozni estri, alkil poliglukozidni (APG) emulgator) kao nosača za poboljšanu (trans)dermalnu isporuku aceklofenaka (model lekovita supstanca iz grupe NSAIL). Preciznije, cilj je bio da se primenom različitih in vitro i in vivo metoda dobije uvid u uticaj varijacija u sastavu formulacije svakog od tipova odabranih nosača (tradicionalni vs. surfaktanti novije generacije, prisustvo vs. odsustvo hemijskih pojačivača penetracije) na dermalnu raspoloţivost aceklofenaka, kao i da se proceni potencijalni značaj primene naprednih sistema, kao što su nanoemulzije, u odnosu na emulzione sisteme koji se jednostavno mogu izraditi u uslovima apoteke. Dodatno, posebno značajno je bilo proceniti da li se kombinovanom primenom nanoemulzija i predtretmana koţe čvrstim mikroiglama, kao fizičkim pojačivačima penetracije, moţe obezbediti poboljšana isporuka aceklofenaka u koţu, odnosno, kroz koţu u sistemsku cirkulaciju.Rezultati sprovedenih istraţivanja nedvosmisleno su ukazali da se primenom kombinovanog smeša-proces eksperimentalnog dizajna mogu uspešno izraditi nanoemulzije aceklofenaka zadovoljavajućih fizičko-hemijskih karakteristika, dugoročne stabilnosti i iritacionog profila korišćenjem biokompatibilnih emulgatora, kao što su lecitin iz jajeta i saharozni estri (prevashodno saharoza palmitat). Dalje, rezultati dobijeni in vitro ispitivanjem oslobaĎanja/permeacije kroz sintetsku membranu/koţu uha svinje, kao i primenom in vitro/in vivo tape stripping metode (sve metode najpre su podvrgnute optimizaciji) ukazali su na superiornost razvijenih nanoemulzija u pogledu isporuke aceklofenaka u/kroz koţu u odnosu na ispitivane mikrostrukturirane emulzione sisteme, istovremeno ukazujući na značajnu ulogu sastavasmeše surfaktanata upotrebljenih za stabilizaciju nanoemulzija u isporuci aceklofenaka u/kroz koţu (saharozni estri su značajno efikasniji kao hemijski penetracioni inhenseri u odnosu na tradicionalno korišćen polisorbat 80)...
AB  - Considering the limited bioavailability and consequently, therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAID) applied on the skin, the aim of present doctoral dissertation was to develop oil-in-water nanoemulsions and conventional (microstructured) emulsions (bases) based on natural polyhydroxy surfactants (sucrose esters, alkyl polyglucoside (APG) emulsifier) as carriers for improved (trans)dermal delivery of aceclofenac (model NSAID) and to comprehensively evaluate their physicochemical and biopharmaceutical properties. Precisely, the present work aimed to evaluate the effect of variations in formulation composition of each selected emulsion system (traditional vs. novel surfactants, presence vs. absence of chemical penetration enhancers) on dermal availability of aceclofenac using different in vitro and in vivo pharmacokinetic-based methods, and thus, to estimate the usefulness of applying the advanced carriers, such as nanoemulsions, compared to the emulsions that can be easily prepared in a pharmacy. Additionally, it was interesting to evaluate whether the combined use of developed nanoemulsions and skin pretreatment with solid stainless steel microneedles (as a physical penetration enhancer) may facilitate aceclofenac delivery into the skin, and/or through the skin into the systemic circulation.Obtained results unequivocally indicated that it was possible to prepare, with the aid of combined mixture-process experimental design, aceclofenac-loaded nanoemulsions with satisfying physicochemical properties, long-term stability and skin irritation profile, using biocompatible emulsifiers, such as egg lecithin and sucrose esters (primarily sucrose palmitate). Furthermore, results obtained using in vitro release/skin permeation tests through the synthetic membrane/pig ear skin as well as in vitro/in vivo tape stripping (all submitted through careful optimization) proved the superiority of developed nanoemulsions regarding aceclofenac delivery into/through the skin compared to tested microstructured emulsion systems, simultaneously singling out the surfactant mixture employed for nanoemulsion stabilization as a key factor for efficientaceclofenac delivery into/through the skin (sucrose esters are more efficient as the chemical penetration enhancers than traditionally used polysorbate 80)...
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Mikro- i nanostrukturirani emulzioni sistemi na bazi polihidroksilnih surfaktanata za isporuku aceklofenaka u/kroz kožu primenom hemijskih pojačivača penetracije i mikroigala
UR  - https://hdl.handle.net/21.15107/rcub_nardus_12186
ER  - 
@phdthesis{
author = "Ilić, Tanja",
year = "2019",
abstract = "Imajući na umu ograničenu biološku raspoloţivost i posledično terapijski efekat nesteroidnih antiinflamatornih lekova (NSAIL) primenjenih na koţi, cilj doktorske disertacije bio je razvoj, optimizacija i sveobuhvatna fizičko-hemijska i biofarmaceutska karakterizacija ulje-u-vodi nanoemulzija, kao i konvencionalnih (mikrostrukturiranih) emulzionih sistema (podloga) na bazi prirodnih polihidroksilnih surfaktanata (saharozni estri, alkil poliglukozidni (APG) emulgator) kao nosača za poboljšanu (trans)dermalnu isporuku aceklofenaka (model lekovita supstanca iz grupe NSAIL). Preciznije, cilj je bio da se primenom različitih in vitro i in vivo metoda dobije uvid u uticaj varijacija u sastavu formulacije svakog od tipova odabranih nosača (tradicionalni vs. surfaktanti novije generacije, prisustvo vs. odsustvo hemijskih pojačivača penetracije) na dermalnu raspoloţivost aceklofenaka, kao i da se proceni potencijalni značaj primene naprednih sistema, kao što su nanoemulzije, u odnosu na emulzione sisteme koji se jednostavno mogu izraditi u uslovima apoteke. Dodatno, posebno značajno je bilo proceniti da li se kombinovanom primenom nanoemulzija i predtretmana koţe čvrstim mikroiglama, kao fizičkim pojačivačima penetracije, moţe obezbediti poboljšana isporuka aceklofenaka u koţu, odnosno, kroz koţu u sistemsku cirkulaciju.Rezultati sprovedenih istraţivanja nedvosmisleno su ukazali da se primenom kombinovanog smeša-proces eksperimentalnog dizajna mogu uspešno izraditi nanoemulzije aceklofenaka zadovoljavajućih fizičko-hemijskih karakteristika, dugoročne stabilnosti i iritacionog profila korišćenjem biokompatibilnih emulgatora, kao što su lecitin iz jajeta i saharozni estri (prevashodno saharoza palmitat). Dalje, rezultati dobijeni in vitro ispitivanjem oslobaĎanja/permeacije kroz sintetsku membranu/koţu uha svinje, kao i primenom in vitro/in vivo tape stripping metode (sve metode najpre su podvrgnute optimizaciji) ukazali su na superiornost razvijenih nanoemulzija u pogledu isporuke aceklofenaka u/kroz koţu u odnosu na ispitivane mikrostrukturirane emulzione sisteme, istovremeno ukazujući na značajnu ulogu sastavasmeše surfaktanata upotrebljenih za stabilizaciju nanoemulzija u isporuci aceklofenaka u/kroz koţu (saharozni estri su značajno efikasniji kao hemijski penetracioni inhenseri u odnosu na tradicionalno korišćen polisorbat 80)..., Considering the limited bioavailability and consequently, therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAID) applied on the skin, the aim of present doctoral dissertation was to develop oil-in-water nanoemulsions and conventional (microstructured) emulsions (bases) based on natural polyhydroxy surfactants (sucrose esters, alkyl polyglucoside (APG) emulsifier) as carriers for improved (trans)dermal delivery of aceclofenac (model NSAID) and to comprehensively evaluate their physicochemical and biopharmaceutical properties. Precisely, the present work aimed to evaluate the effect of variations in formulation composition of each selected emulsion system (traditional vs. novel surfactants, presence vs. absence of chemical penetration enhancers) on dermal availability of aceclofenac using different in vitro and in vivo pharmacokinetic-based methods, and thus, to estimate the usefulness of applying the advanced carriers, such as nanoemulsions, compared to the emulsions that can be easily prepared in a pharmacy. Additionally, it was interesting to evaluate whether the combined use of developed nanoemulsions and skin pretreatment with solid stainless steel microneedles (as a physical penetration enhancer) may facilitate aceclofenac delivery into the skin, and/or through the skin into the systemic circulation.Obtained results unequivocally indicated that it was possible to prepare, with the aid of combined mixture-process experimental design, aceclofenac-loaded nanoemulsions with satisfying physicochemical properties, long-term stability and skin irritation profile, using biocompatible emulsifiers, such as egg lecithin and sucrose esters (primarily sucrose palmitate). Furthermore, results obtained using in vitro release/skin permeation tests through the synthetic membrane/pig ear skin as well as in vitro/in vivo tape stripping (all submitted through careful optimization) proved the superiority of developed nanoemulsions regarding aceclofenac delivery into/through the skin compared to tested microstructured emulsion systems, simultaneously singling out the surfactant mixture employed for nanoemulsion stabilization as a key factor for efficientaceclofenac delivery into/through the skin (sucrose esters are more efficient as the chemical penetration enhancers than traditionally used polysorbate 80)...",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Mikro- i nanostrukturirani emulzioni sistemi na bazi polihidroksilnih surfaktanata za isporuku aceklofenaka u/kroz kožu primenom hemijskih pojačivača penetracije i mikroigala",
url = "https://hdl.handle.net/21.15107/rcub_nardus_12186"
}
Ilić, T.. (2019). Mikro- i nanostrukturirani emulzioni sistemi na bazi polihidroksilnih surfaktanata za isporuku aceklofenaka u/kroz kožu primenom hemijskih pojačivača penetracije i mikroigala. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_12186
Ilić T. Mikro- i nanostrukturirani emulzioni sistemi na bazi polihidroksilnih surfaktanata za isporuku aceklofenaka u/kroz kožu primenom hemijskih pojačivača penetracije i mikroigala. in Универзитет у Београду. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_12186 .
Ilić, Tanja, "Mikro- i nanostrukturirani emulzioni sistemi na bazi polihidroksilnih surfaktanata za isporuku aceklofenaka u/kroz kožu primenom hemijskih pojačivača penetracije i mikroigala" in Универзитет у Београду (2019),
https://hdl.handle.net/21.15107/rcub_nardus_12186 .

Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems

Krajišnik, Danina; Ilić, Tanja; Nikolić, Ines; Savić, Snežana

(Beograd : Savez farmaceutskih udruženja Srbije, 2019)

TY  - JOUR
AU  - Krajišnik, Danina
AU  - Ilić, Tanja
AU  - Nikolić, Ines
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3567
AB  - In the era of modern vaccinology, limited immunogenicity of the most commonly used antigens has enforced the use of various adjuvants in vaccine formulations to achieve desired immune  response.  Aluminum-containing  adjuvants  have  been,  historically,  the  most  widely used mineral immunostimulants, generally regarded as safe to use in human vaccines. The great academic   progress   in   inorganic   (nano)materials   synthesis,   structure   control   and functionalization design has  led  to  a  growing  interest  in innovative  adjuvants  such  as  clays, mesoporous silica nanoparticles, zinc oxide, iron oxide and iron hydroxide nanoparticles, etc. On the other hand, there has been an intention to use specific nanoparticulated antigen delivery systems,  such  as  nanoemulsions,  in  order  to  protect  antigens  from  premature  proteolytic degradation  and/or  to  improve  antigen  immunogenicity  by  facilitating  antigen  uptake  and processing by antigen presenting cells. Simultaneously, numerous research efforts have been focused on the development of innovative technologies for antigen delivery into the skin (such as microneedles), with the aim to improve vaccine efficacy alongside with enhanced patient adherence,  particularly  in  children  population  (noninvasive  or minimally  invasive administration). Therefore, this review deals with each of these approaches in more detail, with the special emphasis on examples of their use in vaccine formulations as well as on the factors influencing their efficacy and safety.
AB  - U  doba  savremene  vakcinologije,  ograničena  imunogenost  većine  korišćenih  antigena podstakla  je  primenu  različitih  adjuvanasa  u  formulacijama  vakcina  radi  postizanja  željenog imunskog odgovora. Mineralni adjuvansi na bazi aluminijuma su istorijski najčešće korišćeni imunostimulansi u vakcinama i smatraju se generalno bezbednim za humanu upotrebu. Značajni napredak  na  polju  sinteze,  kontrole  strukture  i  funkcionalnog  dizajna  neorganskih (nano)materijala uslovio je povećano interesovanje za primenom inovativnih adjuvanasa kao što su  gline,  mezoporozne  silika  nanočestice,  nanočestice  cink-oksida,  gvožđe  oksida  i  gvožđe hidroksida, i dr. Sa druge strane, uočava se i sve veće interesovanje za primenom specifičnih nanonosača  antigena,  kao  što  su  nanoemulzije,  kako  bi  se  antigeni  zaštitili  od  preuranjene proteolitičke  degradacije  i/ili poboljšala  njihova  imunogenost,  olakšavanjem  preuzimanja  i obrade  od  strane  antigen-prezentujućih  ćelija.  Takođe,  brojni  istraživački  napori  tokom poslednjih nekoliko godina usmereni su ka razvoju inovativnih tehnologija za isporuku antigena u kožu (kao što su mikroigle) radi poboljšanja efikasnosti vakcinacije uz istovremeno povećanje adherence pacijenata, posebno u pedijatrijskoj populaciji (neinvazivan ili minimalno invazivan način primene). Otuda, u ovom preglednom radu dat je detaljan pregled karakteristika svakog od  navedenih  pristupa  za  poboljšanje  efikasnosti  vakcina,  sa  posebnim  osvrtom  na  primere njihove primene u formulacijama vakcina i faktore koji određuju efikasnost i bezbednost.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems
T1  - Konvencionalni i napredni adjuvansi u formulacijama vakcina: mineralni adsorbenti, nanočestični nosači i sistemi tipa mikroigala
VL  - 69
IS  - 6
SP  - 420
EP  - 451
DO  - 10.5937/arhfarm1906420K
ER  - 
@article{
author = "Krajišnik, Danina and Ilić, Tanja and Nikolić, Ines and Savić, Snežana",
year = "2019",
abstract = "In the era of modern vaccinology, limited immunogenicity of the most commonly used antigens has enforced the use of various adjuvants in vaccine formulations to achieve desired immune  response.  Aluminum-containing  adjuvants  have  been,  historically,  the  most  widely used mineral immunostimulants, generally regarded as safe to use in human vaccines. The great academic   progress   in   inorganic   (nano)materials   synthesis,   structure   control   and functionalization design has  led  to  a  growing  interest  in innovative  adjuvants  such  as  clays, mesoporous silica nanoparticles, zinc oxide, iron oxide and iron hydroxide nanoparticles, etc. On the other hand, there has been an intention to use specific nanoparticulated antigen delivery systems,  such  as  nanoemulsions,  in  order  to  protect  antigens  from  premature  proteolytic degradation  and/or  to  improve  antigen  immunogenicity  by  facilitating  antigen  uptake  and processing by antigen presenting cells. Simultaneously, numerous research efforts have been focused on the development of innovative technologies for antigen delivery into the skin (such as microneedles), with the aim to improve vaccine efficacy alongside with enhanced patient adherence,  particularly  in  children  population  (noninvasive  or minimally  invasive administration). Therefore, this review deals with each of these approaches in more detail, with the special emphasis on examples of their use in vaccine formulations as well as on the factors influencing their efficacy and safety., U  doba  savremene  vakcinologije,  ograničena  imunogenost  većine  korišćenih  antigena podstakla  je  primenu  različitih  adjuvanasa  u  formulacijama  vakcina  radi  postizanja  željenog imunskog odgovora. Mineralni adjuvansi na bazi aluminijuma su istorijski najčešće korišćeni imunostimulansi u vakcinama i smatraju se generalno bezbednim za humanu upotrebu. Značajni napredak  na  polju  sinteze,  kontrole  strukture  i  funkcionalnog  dizajna  neorganskih (nano)materijala uslovio je povećano interesovanje za primenom inovativnih adjuvanasa kao što su  gline,  mezoporozne  silika  nanočestice,  nanočestice  cink-oksida,  gvožđe  oksida  i  gvožđe hidroksida, i dr. Sa druge strane, uočava se i sve veće interesovanje za primenom specifičnih nanonosača  antigena,  kao  što  su  nanoemulzije,  kako  bi  se  antigeni  zaštitili  od  preuranjene proteolitičke  degradacije  i/ili poboljšala  njihova  imunogenost,  olakšavanjem  preuzimanja  i obrade  od  strane  antigen-prezentujućih  ćelija.  Takođe,  brojni  istraživački  napori  tokom poslednjih nekoliko godina usmereni su ka razvoju inovativnih tehnologija za isporuku antigena u kožu (kao što su mikroigle) radi poboljšanja efikasnosti vakcinacije uz istovremeno povećanje adherence pacijenata, posebno u pedijatrijskoj populaciji (neinvazivan ili minimalno invazivan način primene). Otuda, u ovom preglednom radu dat je detaljan pregled karakteristika svakog od  navedenih  pristupa  za  poboljšanje  efikasnosti  vakcina,  sa  posebnim  osvrtom  na  primere njihove primene u formulacijama vakcina i faktore koji određuju efikasnost i bezbednost.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems, Konvencionalni i napredni adjuvansi u formulacijama vakcina: mineralni adsorbenti, nanočestični nosači i sistemi tipa mikroigala",
volume = "69",
number = "6",
pages = "420-451",
doi = "10.5937/arhfarm1906420K"
}
Krajišnik, D., Ilić, T., Nikolić, I.,& Savić, S.. (2019). Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 69(6), 420-451.
https://doi.org/10.5937/arhfarm1906420K
Krajišnik D, Ilić T, Nikolić I, Savić S. Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems. in Arhiv za farmaciju. 2019;69(6):420-451.
doi:10.5937/arhfarm1906420K .
Krajišnik, Danina, Ilić, Tanja, Nikolić, Ines, Savić, Snežana, "Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems" in Arhiv za farmaciju, 69, no. 6 (2019):420-451,
https://doi.org/10.5937/arhfarm1906420K . .
1
1

Tacrolimus-loaded lecithin-based nanostructured lipid carrier and nanoemulsion with propylene glycol monocaprylate as a liquid lipid: Formulation characterization and assessment of dermal delivery compared to referent ointment

Savić, Vedrana; Ilić, Tanja; Nikolić, Ines; Marković, Bojan; Čalija, Bojan; Cekić, Nebojša; Savić, Snežana

(2019)

TY  - JOUR
AU  - Savić, Vedrana
AU  - Ilić, Tanja
AU  - Nikolić, Ines
AU  - Marković, Bojan
AU  - Čalija, Bojan
AU  - Cekić, Nebojša
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3454
AB  - Nanostructured lipid carriers (NLC) and nanoemulsions (NE) are colloid carriers which could improve dermal delivery of tacrolimus. The aims of this study were to evaluate effects of different formulation and process parameters on physicochemical characteristics and stability of lecithin-based NLC with glyceryl palmitostearate as solid and propylene glycol monocaprylate as liquid lipid and to compare the influence of different inner structure of tacrolimus-loaded NLC and corresponding NE on physicochemical characteristics, stability, entrapment efficiency, in vitro drug release and overall skin performance. Solid/liquid lipid ratio, total amount of lipids, homogenization pressure and cooling after the preparation were identified as critical variables in NLC development. Moreover, tacrolimus-loaded NLC emerged as more stabile carrier than NE. Differential stripping performed on porcine ear skin revealed significantly higher tacrolimus amount in stratum corneum from nanocarriers compared to referent ointment (Protopic®). Similarly the highest amount of tacrolimus in hair follicles was obtained using NLC (268.54 ± 92.38 ng/cm2), followed by NE (128.17 ± 48.87 ng/cm2) and Protopic® (77.61 ± 43.25 ng/cm2). Contrary, the highest permeation rate through full-thickness porcine ear skin was observed for Protopic®, implying that the selection of experimental setup is critical for reliable skin performance assessment. Overall, developed NLC could be suggested as promising carrier in a form of lotion for tacrolimus dermal delivery.
T2  - International Journal of Pharmaceutics
T1  - Tacrolimus-loaded lecithin-based nanostructured lipid carrier and nanoemulsion with propylene glycol monocaprylate as a liquid lipid: Formulation characterization and assessment of dermal delivery compared to referent ointment
VL  - 569
SP  - 1
EP  - 11
DO  - 10.1016/j.ijpharm.2019.118624
ER  - 
@article{
author = "Savić, Vedrana and Ilić, Tanja and Nikolić, Ines and Marković, Bojan and Čalija, Bojan and Cekić, Nebojša and Savić, Snežana",
year = "2019",
abstract = "Nanostructured lipid carriers (NLC) and nanoemulsions (NE) are colloid carriers which could improve dermal delivery of tacrolimus. The aims of this study were to evaluate effects of different formulation and process parameters on physicochemical characteristics and stability of lecithin-based NLC with glyceryl palmitostearate as solid and propylene glycol monocaprylate as liquid lipid and to compare the influence of different inner structure of tacrolimus-loaded NLC and corresponding NE on physicochemical characteristics, stability, entrapment efficiency, in vitro drug release and overall skin performance. Solid/liquid lipid ratio, total amount of lipids, homogenization pressure and cooling after the preparation were identified as critical variables in NLC development. Moreover, tacrolimus-loaded NLC emerged as more stabile carrier than NE. Differential stripping performed on porcine ear skin revealed significantly higher tacrolimus amount in stratum corneum from nanocarriers compared to referent ointment (Protopic®). Similarly the highest amount of tacrolimus in hair follicles was obtained using NLC (268.54 ± 92.38 ng/cm2), followed by NE (128.17 ± 48.87 ng/cm2) and Protopic® (77.61 ± 43.25 ng/cm2). Contrary, the highest permeation rate through full-thickness porcine ear skin was observed for Protopic®, implying that the selection of experimental setup is critical for reliable skin performance assessment. Overall, developed NLC could be suggested as promising carrier in a form of lotion for tacrolimus dermal delivery.",
journal = "International Journal of Pharmaceutics",
title = "Tacrolimus-loaded lecithin-based nanostructured lipid carrier and nanoemulsion with propylene glycol monocaprylate as a liquid lipid: Formulation characterization and assessment of dermal delivery compared to referent ointment",
volume = "569",
pages = "1-11",
doi = "10.1016/j.ijpharm.2019.118624"
}
Savić, V., Ilić, T., Nikolić, I., Marković, B., Čalija, B., Cekić, N.,& Savić, S.. (2019). Tacrolimus-loaded lecithin-based nanostructured lipid carrier and nanoemulsion with propylene glycol monocaprylate as a liquid lipid: Formulation characterization and assessment of dermal delivery compared to referent ointment. in International Journal of Pharmaceutics, 569, 1-11.
https://doi.org/10.1016/j.ijpharm.2019.118624
Savić V, Ilić T, Nikolić I, Marković B, Čalija B, Cekić N, Savić S. Tacrolimus-loaded lecithin-based nanostructured lipid carrier and nanoemulsion with propylene glycol monocaprylate as a liquid lipid: Formulation characterization and assessment of dermal delivery compared to referent ointment. in International Journal of Pharmaceutics. 2019;569:1-11.
doi:10.1016/j.ijpharm.2019.118624 .
Savić, Vedrana, Ilić, Tanja, Nikolić, Ines, Marković, Bojan, Čalija, Bojan, Cekić, Nebojša, Savić, Snežana, "Tacrolimus-loaded lecithin-based nanostructured lipid carrier and nanoemulsion with propylene glycol monocaprylate as a liquid lipid: Formulation characterization and assessment of dermal delivery compared to referent ointment" in International Journal of Pharmaceutics, 569 (2019):1-11,
https://doi.org/10.1016/j.ijpharm.2019.118624 . .
29
11
27

Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form

Bubić Pajić, Nataša; Ilić, Tanja; Nikolić, Ines; Dobričić, Vladimir; Pantelić, Ivana; Savić, Snežana

(2019)

TY  - JOUR
AU  - Bubić Pajić, Nataša
AU  - Ilić, Tanja
AU  - Nikolić, Ines
AU  - Dobričić, Vladimir
AU  - Pantelić, Ivana
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3453
AB  - Aiming to develop biocompatible microemulsions based on natural alkyl polyglucoside surfactant as prospective carriers for improved dermal delivery of adapalene, phase behavior and microstructure of pseudo-ternary oil/decyl glucoside/propylene glycol/water systems were evaluated. The chosen inverted bicontinuous formulations did not change their microstructure upon drug incorporation and remained stable during 1-year period. Preliminary in vivo assessment of skin performances suggested satisfying safety profiles of placebo microemulsions, in spite of considerable changes in skin hydration and barrier function. Interestingly, despite lower in vitro drug release, the amount of adapalene penetrated into porcine skin under infinite dosing regime was higher from microemulsions than from commercial drug product, reaching dermal retention enhancement ratio of 5.9. However, by changing experimental conditions to the more realistic in-use situation, the amount of adapalene extracted from the stratum corneum was comparable for microemulsions and marketed product. Similarly, the drug deposition in hair follicles was slightly pronounced with novel microemulsion vehicles (183.30 ± 156.32 ng/cm2 and 167.39 ± 108.96 ng/cm2 vs. 157.00 ± 114.91 ng/cm2), highlighting the importance of proper selection of experimental conditions when assessing trans(dermal) drug delivery. Consequently, our results suggest that alkyl polyglucoside based microemulsions are promising vehicles worth exploring further for targeted intraderdermal delivery of adapalene in acne treatment.
T2  - Journal of Drug Delivery Science and Technology
T1  - Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form
VL  - 54
SP  - 1
EP  - 12
DO  - 10.1016/j.jddst.2019.101245
ER  - 
@article{
author = "Bubić Pajić, Nataša and Ilić, Tanja and Nikolić, Ines and Dobričić, Vladimir and Pantelić, Ivana and Savić, Snežana",
year = "2019",
abstract = "Aiming to develop biocompatible microemulsions based on natural alkyl polyglucoside surfactant as prospective carriers for improved dermal delivery of adapalene, phase behavior and microstructure of pseudo-ternary oil/decyl glucoside/propylene glycol/water systems were evaluated. The chosen inverted bicontinuous formulations did not change their microstructure upon drug incorporation and remained stable during 1-year period. Preliminary in vivo assessment of skin performances suggested satisfying safety profiles of placebo microemulsions, in spite of considerable changes in skin hydration and barrier function. Interestingly, despite lower in vitro drug release, the amount of adapalene penetrated into porcine skin under infinite dosing regime was higher from microemulsions than from commercial drug product, reaching dermal retention enhancement ratio of 5.9. However, by changing experimental conditions to the more realistic in-use situation, the amount of adapalene extracted from the stratum corneum was comparable for microemulsions and marketed product. Similarly, the drug deposition in hair follicles was slightly pronounced with novel microemulsion vehicles (183.30 ± 156.32 ng/cm2 and 167.39 ± 108.96 ng/cm2 vs. 157.00 ± 114.91 ng/cm2), highlighting the importance of proper selection of experimental conditions when assessing trans(dermal) drug delivery. Consequently, our results suggest that alkyl polyglucoside based microemulsions are promising vehicles worth exploring further for targeted intraderdermal delivery of adapalene in acne treatment.",
journal = "Journal of Drug Delivery Science and Technology",
title = "Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form",
volume = "54",
pages = "1-12",
doi = "10.1016/j.jddst.2019.101245"
}
Bubić Pajić, N., Ilić, T., Nikolić, I., Dobričić, V., Pantelić, I.,& Savić, S.. (2019). Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form. in Journal of Drug Delivery Science and Technology, 54, 1-12.
https://doi.org/10.1016/j.jddst.2019.101245
Bubić Pajić N, Ilić T, Nikolić I, Dobričić V, Pantelić I, Savić S. Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form. in Journal of Drug Delivery Science and Technology. 2019;54:1-12.
doi:10.1016/j.jddst.2019.101245 .
Bubić Pajić, Nataša, Ilić, Tanja, Nikolić, Ines, Dobričić, Vladimir, Pantelić, Ivana, Savić, Snežana, "Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form" in Journal of Drug Delivery Science and Technology, 54 (2019):1-12,
https://doi.org/10.1016/j.jddst.2019.101245 . .
12
7
13

Biopharmaceutical properties of adapalene loaded biocompatible microemulsions

Bubić Pajić, Nataša; Nikolić, Ines; Dobričić, Vladimir; Savić, Snežana

(2019)

TY  - CONF
AU  - Bubić Pajić, Nataša
AU  - Nikolić, Ines
AU  - Dobričić, Vladimir
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5456
AB  - Adapalene (ADA) belongs to the group of retinoids,
synthetic analogs of retinol, and it is used as a first line
therapy of mild to moderate acne, with a few exceptions
(1). However, dermal availability of ADA is limited due to
its poor aqueous solubility. In order to enhance the drug
penetration into target areas (i.e. hair follicles and
epidermis), several strategies, such as liposomes,
microemulsions (MEs), solid lipid microparticles,
nanostructured lipid carriers etc., were proposed recently.
MEs have been reported as a promising tool for topical drug
delivery because they combine several advantages over
conventional formulations, including ease of manufacture,
high solubilization potential for poorly soluble drugs,
reduced side effects, long-term stability and improved drug
penetration through/into the skin (2).
C3  - 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book
T1  - Biopharmaceutical properties of adapalene loaded biocompatible microemulsions
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5456
ER  - 
@conference{
author = "Bubić Pajić, Nataša and Nikolić, Ines and Dobričić, Vladimir and Savić, Snežana",
year = "2019",
abstract = "Adapalene (ADA) belongs to the group of retinoids,
synthetic analogs of retinol, and it is used as a first line
therapy of mild to moderate acne, with a few exceptions
(1). However, dermal availability of ADA is limited due to
its poor aqueous solubility. In order to enhance the drug
penetration into target areas (i.e. hair follicles and
epidermis), several strategies, such as liposomes,
microemulsions (MEs), solid lipid microparticles,
nanostructured lipid carriers etc., were proposed recently.
MEs have been reported as a promising tool for topical drug
delivery because they combine several advantages over
conventional formulations, including ease of manufacture,
high solubilization potential for poorly soluble drugs,
reduced side effects, long-term stability and improved drug
penetration through/into the skin (2).",
journal = "3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book",
title = "Biopharmaceutical properties of adapalene loaded biocompatible microemulsions",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5456"
}
Bubić Pajić, N., Nikolić, I., Dobričić, V.,& Savić, S.. (2019). Biopharmaceutical properties of adapalene loaded biocompatible microemulsions. in 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book.
https://hdl.handle.net/21.15107/rcub_farfar_5456
Bubić Pajić N, Nikolić I, Dobričić V, Savić S. Biopharmaceutical properties of adapalene loaded biocompatible microemulsions. in 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_5456 .
Bubić Pajić, Nataša, Nikolić, Ines, Dobričić, Vladimir, Savić, Snežana, "Biopharmaceutical properties of adapalene loaded biocompatible microemulsions" in 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book (2019),
https://hdl.handle.net/21.15107/rcub_farfar_5456 .

Degradation kinetics and characterization of degradation products of losartan potassium by lc-ms/ms method

Dobričić, Vladimir; Marković, Bojan

(Pharmaceutical Association of Serbia, 2019)

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Marković, Bojan
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3665
AB  - U  ovom  radu  opisano  je  ispitivanje  stabilnosti  losartan  kalijuma  primenom  tečne hromatografije sa UV i MS-MS detekcijom i prikazan je njegov profil degradacionih proizvoda. Rastvor  losartan  kalijuma  bio  je  izložen  dejstvu  sledećih  stres  agenasa:  0,1  M  HCl;                       0,1 M NaOH i 3% (v/v) H2O2. Rastvori losartan kalijuma analizirani su gradijentnim eluiranjem sa  acetonitrilom  i  0,1%  (v/v)  vodenim  rastvorom  CF3COOH  pri  konstantnom protoku  od    0,5 ml min-1 i vremenom trajanja od 22 min. Degradacija u rastvorima losartan kalijuma koji su 7 dana bili izloženi dejstvu 0,1 M HCl i 0,1 M NaOH bila je manja od 1%, dok je u prisustvu 3% (v/v) H2O2 bila značajno veća (oko 10%).  Identifikacija  i  strukturna  analiza  glavnih  degradacionih  proizvoda  losartan  kalijuma izvršena je primenom LC-MS/MS metode. Grafička  zavisnost  izmerenih  koncentracija  u  funkciji  vremena  ukazuje  da  se  losartan kalijum  u  rastvoru  3%  (v/v)  H2O2  degradira  kinetikom  pseudo nultog  reda  sa  konstantnom brzine reakcije od 1.48ꞏ10-8 mol L-1 dan-1.
AB  - This paper presents study of losartan potassium stability evaluation by liquid chromatography with UV/VIS and MS-MS detection and its degradation profile. A solution of losartan potassium was exposed to the following stress agents: 0.1 M HCl, 0.1 M NaOH, and 3% (v/v) H2O2. The analyses of losartan potassium solutions were carried out in a gradient elution mode with acetonitrile and 0.1% (v/v) CF3COOH aqueous solution and constant flow rate of 0.5 mL min-1 within 22 min run time. After 7 days of losartan potassium solutions exposure to the stress agents at room temperature, it was found that the degree of degradation in the presence of 0.1 M HCl and 0.1 M NaOH was less than 1%, while in the presence of 3% H2O2 degradation was significantly higher (about 10%). Chemical structure elucidation of the major degradation products of losartan potassium was performed using LC-MS/MS method. The concentration versus time plot indicated that in 3% (v/v) H2O2 solution losartan potassium was degraded according to the pseudo zero-order reaction kinetics with 1.4810-8 mol L-1 day-1 rate constant. © 2019, Pharmaceutical Association of Serbia. All rights reserved.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Degradation kinetics and characterization of degradation products of losartan potassium by lc-ms/ms method
T1  - Kinetika degradacije i karakterizacija degradacionih proizvoda losartan kalijuma lcms/ms metodom
VL  - 69
IS  - 2
SP  - 80
EP  - 89
DO  - 10.5937/arhfarm1902080X
ER  - 
@article{
author = "Dobričić, Vladimir and Marković, Bojan",
year = "2019",
abstract = "U  ovom  radu  opisano  je  ispitivanje  stabilnosti  losartan  kalijuma  primenom  tečne hromatografije sa UV i MS-MS detekcijom i prikazan je njegov profil degradacionih proizvoda. Rastvor  losartan  kalijuma  bio  je  izložen  dejstvu  sledećih  stres  agenasa:  0,1  M  HCl;                       0,1 M NaOH i 3% (v/v) H2O2. Rastvori losartan kalijuma analizirani su gradijentnim eluiranjem sa  acetonitrilom  i  0,1%  (v/v)  vodenim  rastvorom  CF3COOH  pri  konstantnom protoku  od    0,5 ml min-1 i vremenom trajanja od 22 min. Degradacija u rastvorima losartan kalijuma koji su 7 dana bili izloženi dejstvu 0,1 M HCl i 0,1 M NaOH bila je manja od 1%, dok je u prisustvu 3% (v/v) H2O2 bila značajno veća (oko 10%).  Identifikacija  i  strukturna  analiza  glavnih  degradacionih  proizvoda  losartan  kalijuma izvršena je primenom LC-MS/MS metode. Grafička  zavisnost  izmerenih  koncentracija  u  funkciji  vremena  ukazuje  da  se  losartan kalijum  u  rastvoru  3%  (v/v)  H2O2  degradira  kinetikom  pseudo nultog  reda  sa  konstantnom brzine reakcije od 1.48ꞏ10-8 mol L-1 dan-1., This paper presents study of losartan potassium stability evaluation by liquid chromatography with UV/VIS and MS-MS detection and its degradation profile. A solution of losartan potassium was exposed to the following stress agents: 0.1 M HCl, 0.1 M NaOH, and 3% (v/v) H2O2. The analyses of losartan potassium solutions were carried out in a gradient elution mode with acetonitrile and 0.1% (v/v) CF3COOH aqueous solution and constant flow rate of 0.5 mL min-1 within 22 min run time. After 7 days of losartan potassium solutions exposure to the stress agents at room temperature, it was found that the degree of degradation in the presence of 0.1 M HCl and 0.1 M NaOH was less than 1%, while in the presence of 3% H2O2 degradation was significantly higher (about 10%). Chemical structure elucidation of the major degradation products of losartan potassium was performed using LC-MS/MS method. The concentration versus time plot indicated that in 3% (v/v) H2O2 solution losartan potassium was degraded according to the pseudo zero-order reaction kinetics with 1.4810-8 mol L-1 day-1 rate constant. © 2019, Pharmaceutical Association of Serbia. All rights reserved.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Degradation kinetics and characterization of degradation products of losartan potassium by lc-ms/ms method, Kinetika degradacije i karakterizacija degradacionih proizvoda losartan kalijuma lcms/ms metodom",
volume = "69",
number = "2",
pages = "80-89",
doi = "10.5937/arhfarm1902080X"
}
Dobričić, V.,& Marković, B.. (2019). Degradation kinetics and characterization of degradation products of losartan potassium by lc-ms/ms method. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 69(2), 80-89.
https://doi.org/10.5937/arhfarm1902080X
Dobričić V, Marković B. Degradation kinetics and characterization of degradation products of losartan potassium by lc-ms/ms method. in Arhiv za farmaciju. 2019;69(2):80-89.
doi:10.5937/arhfarm1902080X .
Dobričić, Vladimir, Marković, Bojan, "Degradation kinetics and characterization of degradation products of losartan potassium by lc-ms/ms method" in Arhiv za farmaciju, 69, no. 2 (2019):80-89,
https://doi.org/10.5937/arhfarm1902080X . .
2
2

Izazovi in vitro karakterizacije nebioloških kompleksnih lekova - primer parenteralnih preparata sa liposomskim nosačima lekovitih supstanci

Krajišnik, Danina; Milić, Jela; Savić, Snežana

(Beograd : Savez farmaceutskih udruženja Srbije, 2019)

TY  - JOUR
AU  - Krajišnik, Danina
AU  - Milić, Jela
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3490
AB  - Parenteralnim  putem  se  primenjuju  različiti  tipovi  farmaceutskih  preparata  čiji  sastav može  biti  jednostavan  (vodeni  rastvori)  i  manje  ili  više  kompleksan  (emulzije,  suspenzije, liposomi kao nosači lekovitih supstanci, čestični sistemi, čvrsti implanti/implantati). Napredak u bio-  i  nanotehnologiji  omogućio  je  razvoj  nove  klase  kompleksnih  lekova,  bioloških  i  tzv. nebioloških  kompleksnih  lekova  (i  njihovih  „similara”-  sličnih lekova),  čiji  dalji  razvoj  se očekuje u bliskoj budućnosti, a  koji se, u velikom broju slučajeva, primenjuju parenteralnim putem.  Parenteralni preparati koji u svom sastavu sadrže lekovite supstance koje su inkapsulirane u nosače tipa liposoma predstavljaju nebiološke kompleksne lekove koji su do sada najduže u upotrebi i čije su osobine i definisana svojstva kvaliteta najviše ispitivana. U radu je dat pregled obaveznih  i  dodatnih  (specifičnih) in  vitro  ispitivanja  liposomskih  nosača  lekovitih supstanci za primenu parenteralnim putem. Činjenica da postupci izvođenja ovih ispitivanja u  osnovi  nisu  propisani  u  relevantnim  farmakopejama  (Ph.  Eur., USP  i  JP)  i  da  se  mogu značajno razlikovati između laboratorija, doprinosi velikoj varijabilnosti dobijenih rezultata i ograničenjima u njihovom međusobnom poređenju. Regulatorna tela EMA i FDA učestvovala su u pripremi određenih dokumenata i razvoju odgovarajućih standarda i smernica u pogledu ispitivanja  kvaliteta  farmaceutskih  oblika  sa  liposomskim  nosačima  lekovitih  supstanci  za parenteralnu primenu.
AB  - A greater variety of pharmaceutical preparations can be administered by the parenteral route, the composition of which can be simple (aqueous solutions) and more or less complex (emulsions,  suspensions,  liposomes  as  carriers  of  active  pharmaceutical  ingredients,  particle systems,  solid  implants/implants).  In  addition,  advances  in  bio-  and  nano-  technology  have enabled the development of new classes of complex drugs, so-called non-biological complex drugs (and their similars) whose further development is expected in the near future, and which are in many cases applied by parenteral route.  Parenteral preparations containing active substances encapsulated in the liposome-type carriers represent a class of non-biological complex drugs which have the longest use so far and whose properties and defined quality characteristics are being most examined. In this paper, an overview  of  mandatory  and  additional  (specific) in  vitro  tests  for  parenteral  liposomal  drug carriers is presented. The fact that standard testing procedures are often not available in relevant pharmacopoeias  (Ph.  Eur.,  USP  and  JP),  so  that  they  can  vary  significantly  between laboratories, contributes to the great variability of the results obtained and constraints in their mutual  comparison.  EMA  and  FDA,  as  regulatory  agencies,  have  also  participated  in  the preparation of certain documents and development of appropriate standards and guidelines for quality control of liposomal drug carriers for parenteral application.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Izazovi in vitro karakterizacije nebioloških kompleksnih lekova - primer parenteralnih preparata sa liposomskim nosačima lekovitih supstanci
T1  - Challenges of in vitro characterization of non-biological complex drugs - example of parenteral preparations with liposomal drug carriers
VL  - 69
IS  - 3
SP  - 176
EP  - 198
DO  - 10.5937/arhfarm1903176K
ER  - 
@article{
author = "Krajišnik, Danina and Milić, Jela and Savić, Snežana",
year = "2019",
abstract = "Parenteralnim  putem  se  primenjuju  različiti  tipovi  farmaceutskih  preparata  čiji  sastav može  biti  jednostavan  (vodeni  rastvori)  i  manje  ili  više  kompleksan  (emulzije,  suspenzije, liposomi kao nosači lekovitih supstanci, čestični sistemi, čvrsti implanti/implantati). Napredak u bio-  i  nanotehnologiji  omogućio  je  razvoj  nove  klase  kompleksnih  lekova,  bioloških  i  tzv. nebioloških  kompleksnih  lekova  (i  njihovih  „similara”-  sličnih lekova),  čiji  dalji  razvoj  se očekuje u bliskoj budućnosti, a  koji se, u velikom broju slučajeva, primenjuju parenteralnim putem.  Parenteralni preparati koji u svom sastavu sadrže lekovite supstance koje su inkapsulirane u nosače tipa liposoma predstavljaju nebiološke kompleksne lekove koji su do sada najduže u upotrebi i čije su osobine i definisana svojstva kvaliteta najviše ispitivana. U radu je dat pregled obaveznih  i  dodatnih  (specifičnih) in  vitro  ispitivanja  liposomskih  nosača  lekovitih supstanci za primenu parenteralnim putem. Činjenica da postupci izvođenja ovih ispitivanja u  osnovi  nisu  propisani  u  relevantnim  farmakopejama  (Ph.  Eur., USP  i  JP)  i  da  se  mogu značajno razlikovati između laboratorija, doprinosi velikoj varijabilnosti dobijenih rezultata i ograničenjima u njihovom međusobnom poređenju. Regulatorna tela EMA i FDA učestvovala su u pripremi određenih dokumenata i razvoju odgovarajućih standarda i smernica u pogledu ispitivanja  kvaliteta  farmaceutskih  oblika  sa  liposomskim  nosačima  lekovitih  supstanci  za parenteralnu primenu., A greater variety of pharmaceutical preparations can be administered by the parenteral route, the composition of which can be simple (aqueous solutions) and more or less complex (emulsions,  suspensions,  liposomes  as  carriers  of  active  pharmaceutical  ingredients,  particle systems,  solid  implants/implants).  In  addition,  advances  in  bio-  and  nano-  technology  have enabled the development of new classes of complex drugs, so-called non-biological complex drugs (and their similars) whose further development is expected in the near future, and which are in many cases applied by parenteral route.  Parenteral preparations containing active substances encapsulated in the liposome-type carriers represent a class of non-biological complex drugs which have the longest use so far and whose properties and defined quality characteristics are being most examined. In this paper, an overview  of  mandatory  and  additional  (specific) in  vitro  tests  for  parenteral  liposomal  drug carriers is presented. The fact that standard testing procedures are often not available in relevant pharmacopoeias  (Ph.  Eur.,  USP  and  JP),  so  that  they  can  vary  significantly  between laboratories, contributes to the great variability of the results obtained and constraints in their mutual  comparison.  EMA  and  FDA,  as  regulatory  agencies,  have  also  participated  in  the preparation of certain documents and development of appropriate standards and guidelines for quality control of liposomal drug carriers for parenteral application.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Izazovi in vitro karakterizacije nebioloških kompleksnih lekova - primer parenteralnih preparata sa liposomskim nosačima lekovitih supstanci, Challenges of in vitro characterization of non-biological complex drugs - example of parenteral preparations with liposomal drug carriers",
volume = "69",
number = "3",
pages = "176-198",
doi = "10.5937/arhfarm1903176K"
}
Krajišnik, D., Milić, J.,& Savić, S.. (2019). Izazovi in vitro karakterizacije nebioloških kompleksnih lekova - primer parenteralnih preparata sa liposomskim nosačima lekovitih supstanci. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 69(3), 176-198.
https://doi.org/10.5937/arhfarm1903176K
Krajišnik D, Milić J, Savić S. Izazovi in vitro karakterizacije nebioloških kompleksnih lekova - primer parenteralnih preparata sa liposomskim nosačima lekovitih supstanci. in Arhiv za farmaciju. 2019;69(3):176-198.
doi:10.5937/arhfarm1903176K .
Krajišnik, Danina, Milić, Jela, Savić, Snežana, "Izazovi in vitro karakterizacije nebioloških kompleksnih lekova - primer parenteralnih preparata sa liposomskim nosačima lekovitih supstanci" in Arhiv za farmaciju, 69, no. 3 (2019):176-198,
https://doi.org/10.5937/arhfarm1903176K . .

Development of polysaccharide-based mucoadhesive ophthalmic lubricating vehicles: The effect of different polymers on physicochemical properties and functionality

Račić, Anđelka; Čalija, Bojan; Milić, Jela; Milasinvić, Nikola; Krajišnik, Danina

(Elsevier Science BV, Amsterdam, 2019)

TY  - JOUR
AU  - Račić, Anđelka
AU  - Čalija, Bojan
AU  - Milić, Jela
AU  - Milasinvić, Nikola
AU  - Krajišnik, Danina
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3330
AB  - Incorporation of mucoadhesive polymers is one of the first efficient modification of conventional liquid ophthalmic formulations in order to prolong the residence time at ocular surface. The aim of this work was formulation of viscous ophthalmic vehicles/ocular lubricants containing derivative of guar gum, chitosan and cellulose derivatives (hypromellose and hydroxyethylcellulose) alone or in combination. Optimized formulations were developed by choosing appropriate polymer or combination of polymers in suitable concentrations with adequate physicochemical, rheological and mucoadhesive properties. Influence of the addition of simulated tear fluid, steam sterilization and storage on clarity, pH value and rheological properties of different formulations were evaluated. The compounded vehicles were compared with commercially available ocular lubricants containing similar polymers. It was observed that viscosities of commercially available eye drops were above the optimal viscosity range. The mucoadhesive potential of the vehicles, rheological synergism and type of polymermucin interaction were determined. Combination of chitosan and guar gum exhibited optimal physicochemical, rheological and mucoadhesive properties and had a potential for the longest retention time in tear film. Considering the simplicity of its preparation and stability (over a period of one-month storage), this vehicle could be used for extemporaneously compounded ocular preparations for specific needs of individual patients.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Drug Delivery Science and Technology
T1  - Development of polysaccharide-based mucoadhesive ophthalmic lubricating vehicles: The effect of different polymers on physicochemical properties and functionality
VL  - 49
SP  - 50
EP  - 57
DO  - 10.1016/j.jddst.2018.10.034
ER  - 
@article{
author = "Račić, Anđelka and Čalija, Bojan and Milić, Jela and Milasinvić, Nikola and Krajišnik, Danina",
year = "2019",
abstract = "Incorporation of mucoadhesive polymers is one of the first efficient modification of conventional liquid ophthalmic formulations in order to prolong the residence time at ocular surface. The aim of this work was formulation of viscous ophthalmic vehicles/ocular lubricants containing derivative of guar gum, chitosan and cellulose derivatives (hypromellose and hydroxyethylcellulose) alone or in combination. Optimized formulations were developed by choosing appropriate polymer or combination of polymers in suitable concentrations with adequate physicochemical, rheological and mucoadhesive properties. Influence of the addition of simulated tear fluid, steam sterilization and storage on clarity, pH value and rheological properties of different formulations were evaluated. The compounded vehicles were compared with commercially available ocular lubricants containing similar polymers. It was observed that viscosities of commercially available eye drops were above the optimal viscosity range. The mucoadhesive potential of the vehicles, rheological synergism and type of polymermucin interaction were determined. Combination of chitosan and guar gum exhibited optimal physicochemical, rheological and mucoadhesive properties and had a potential for the longest retention time in tear film. Considering the simplicity of its preparation and stability (over a period of one-month storage), this vehicle could be used for extemporaneously compounded ocular preparations for specific needs of individual patients.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Drug Delivery Science and Technology",
title = "Development of polysaccharide-based mucoadhesive ophthalmic lubricating vehicles: The effect of different polymers on physicochemical properties and functionality",
volume = "49",
pages = "50-57",
doi = "10.1016/j.jddst.2018.10.034"
}
Račić, A., Čalija, B., Milić, J., Milasinvić, N.,& Krajišnik, D.. (2019). Development of polysaccharide-based mucoadhesive ophthalmic lubricating vehicles: The effect of different polymers on physicochemical properties and functionality. in Journal of Drug Delivery Science and Technology
Elsevier Science BV, Amsterdam., 49, 50-57.
https://doi.org/10.1016/j.jddst.2018.10.034
Račić A, Čalija B, Milić J, Milasinvić N, Krajišnik D. Development of polysaccharide-based mucoadhesive ophthalmic lubricating vehicles: The effect of different polymers on physicochemical properties and functionality. in Journal of Drug Delivery Science and Technology. 2019;49:50-57.
doi:10.1016/j.jddst.2018.10.034 .
Račić, Anđelka, Čalija, Bojan, Milić, Jela, Milasinvić, Nikola, Krajišnik, Danina, "Development of polysaccharide-based mucoadhesive ophthalmic lubricating vehicles: The effect of different polymers on physicochemical properties and functionality" in Journal of Drug Delivery Science and Technology, 49 (2019):50-57,
https://doi.org/10.1016/j.jddst.2018.10.034 . .
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25

Synthesis and characterization of polyaniline/BEA zeolite composites and their application in nicosulfuron adsorption

Jevremović, Anka; Bober, Patrycja; Mičušík, Matej; Kuliček, Jaroslav; Acharya, Udit; Pfleger, Jiří; Milojević-Rakić, Maja; Krajišnik, Danina; Trchova, Miroslava; Stejskal, Jaroslav; Ćirić-Marjanović, Gordana

(Elsevier B.V., 2019)

TY  - JOUR
AU  - Jevremović, Anka
AU  - Bober, Patrycja
AU  - Mičušík, Matej
AU  - Kuliček, Jaroslav
AU  - Acharya, Udit
AU  - Pfleger, Jiří
AU  - Milojević-Rakić, Maja
AU  - Krajišnik, Danina
AU  - Trchova, Miroslava
AU  - Stejskal, Jaroslav
AU  - Ćirić-Marjanović, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3248
AB  - Composite materials of BEA zeolite and polyaniline (PANI) were prepared by the chemical oxidative polymerization of aniline in the presence of zeolite in water (without added acid) and in an aqueous solution of sulfuric acid, using ammonium peroxydisulfate as an oxidant. Protonated (as-synthesized) and deprotonated forms of the composites and pristine PANIs were characterized by scanning electron microscopy, conductivity and zeta potential measurements, FTIR, Raman and XPS spectroscopies, and thermogravimetric analysis. Adsorption properties of synthesized materials for removal of nicosulfuron pesticide from aqueous solutions were studied, using HPLC technique. The obtained adsorption isotherms were analyzed using Freundlich and Langmuir-Freundlich equations. Protonated PANI/BEA composites showed excellent adsorption capacity (18.4–25.4 mg g−1), that was higher than the adsorption capacity of pristine BEA zeolite (18.2 mg g−1) but slightly less than neat PANI. Among PANIs, the highest adsorption capacity of 29.8 mg g−1 of adsorbent was found for protonated PANI prepared in sulfuric acid solution. Analysis of adsorption isotherms revealed high degree of surface homogeneity for all prepared composite materials and PANIs. Proposed mechanism for enhanced adsorption of nicosulfuron on protonated composites is based on hydrogen bonding of nicosulfuron O- and N-containing groups with bridging hydroxyls of BEA zeolite and –NH/ = NH+/−NH•+ groups in protonated emeraldine salt form of PANI chains (PANI-ES), accompanied with electrostatic attractive interaction between anionic nicosulfuron species and positive = NH+/−NH•+ groups in bipolaron/polaron containing structures of PANI-ES. Presence of protons in bridging hydroxyls in BEA zeolite and in protonated PANI-ES chains is essential for excellent adsorption of nicosulfuron via hydrogen bonding on all protonated composite samples. In support of this interpretation, deprotonated PANI/BEA composites and deprotonated PANIs showed significantly lower adsorption capacities (in the range 5.5–13.0 mg g−1) compared to those of their protonated counterparts.
PB  - Elsevier B.V.
T2  - Microporous and Mesoporous Materials
T1  - Synthesis and characterization of polyaniline/BEA zeolite composites and their application in nicosulfuron adsorption
SP  - 234
EP  - 245
DO  - 10.1016/j.micromeso.2019.06.006
ER  - 
@article{
author = "Jevremović, Anka and Bober, Patrycja and Mičušík, Matej and Kuliček, Jaroslav and Acharya, Udit and Pfleger, Jiří and Milojević-Rakić, Maja and Krajišnik, Danina and Trchova, Miroslava and Stejskal, Jaroslav and Ćirić-Marjanović, Gordana",
year = "2019",
abstract = "Composite materials of BEA zeolite and polyaniline (PANI) were prepared by the chemical oxidative polymerization of aniline in the presence of zeolite in water (without added acid) and in an aqueous solution of sulfuric acid, using ammonium peroxydisulfate as an oxidant. Protonated (as-synthesized) and deprotonated forms of the composites and pristine PANIs were characterized by scanning electron microscopy, conductivity and zeta potential measurements, FTIR, Raman and XPS spectroscopies, and thermogravimetric analysis. Adsorption properties of synthesized materials for removal of nicosulfuron pesticide from aqueous solutions were studied, using HPLC technique. The obtained adsorption isotherms were analyzed using Freundlich and Langmuir-Freundlich equations. Protonated PANI/BEA composites showed excellent adsorption capacity (18.4–25.4 mg g−1), that was higher than the adsorption capacity of pristine BEA zeolite (18.2 mg g−1) but slightly less than neat PANI. Among PANIs, the highest adsorption capacity of 29.8 mg g−1 of adsorbent was found for protonated PANI prepared in sulfuric acid solution. Analysis of adsorption isotherms revealed high degree of surface homogeneity for all prepared composite materials and PANIs. Proposed mechanism for enhanced adsorption of nicosulfuron on protonated composites is based on hydrogen bonding of nicosulfuron O- and N-containing groups with bridging hydroxyls of BEA zeolite and –NH/ = NH+/−NH•+ groups in protonated emeraldine salt form of PANI chains (PANI-ES), accompanied with electrostatic attractive interaction between anionic nicosulfuron species and positive = NH+/−NH•+ groups in bipolaron/polaron containing structures of PANI-ES. Presence of protons in bridging hydroxyls in BEA zeolite and in protonated PANI-ES chains is essential for excellent adsorption of nicosulfuron via hydrogen bonding on all protonated composite samples. In support of this interpretation, deprotonated PANI/BEA composites and deprotonated PANIs showed significantly lower adsorption capacities (in the range 5.5–13.0 mg g−1) compared to those of their protonated counterparts.",
publisher = "Elsevier B.V.",
journal = "Microporous and Mesoporous Materials",
title = "Synthesis and characterization of polyaniline/BEA zeolite composites and their application in nicosulfuron adsorption",
pages = "234-245",
doi = "10.1016/j.micromeso.2019.06.006"
}
Jevremović, A., Bober, P., Mičušík, M., Kuliček, J., Acharya, U., Pfleger, J., Milojević-Rakić, M., Krajišnik, D., Trchova, M., Stejskal, J.,& Ćirić-Marjanović, G.. (2019). Synthesis and characterization of polyaniline/BEA zeolite composites and their application in nicosulfuron adsorption. in Microporous and Mesoporous Materials
Elsevier B.V.., 234-245.
https://doi.org/10.1016/j.micromeso.2019.06.006
Jevremović A, Bober P, Mičušík M, Kuliček J, Acharya U, Pfleger J, Milojević-Rakić M, Krajišnik D, Trchova M, Stejskal J, Ćirić-Marjanović G. Synthesis and characterization of polyaniline/BEA zeolite composites and their application in nicosulfuron adsorption. in Microporous and Mesoporous Materials. 2019;:234-245.
doi:10.1016/j.micromeso.2019.06.006 .
Jevremović, Anka, Bober, Patrycja, Mičušík, Matej, Kuliček, Jaroslav, Acharya, Udit, Pfleger, Jiří, Milojević-Rakić, Maja, Krajišnik, Danina, Trchova, Miroslava, Stejskal, Jaroslav, Ćirić-Marjanović, Gordana, "Synthesis and characterization of polyaniline/BEA zeolite composites and their application in nicosulfuron adsorption" in Microporous and Mesoporous Materials (2019):234-245,
https://doi.org/10.1016/j.micromeso.2019.06.006 . .
1
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In silico investigation of the relation between calcium channel blockers’ molecular descriptors and oral bioavailability data

Odović, Jadranka

(Bulgarian Academy of Sciences, 2019)

TY  - JOUR
AU  - Odović, Jadranka
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3285
AB  - Calcium channel blockers are commonly prescribed antihypertensive drugs. In this study, nine calcium channel blockers (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem) were investigated to evaluate the relationship between their molecular properties and oral bioavailability data collected from relevant literature. Several molecular descriptors of calcium channel blockers: lipophilicity descriptors, different logP values (AlogPs, AClogP, AB/logP, milogP, AlogP, MlogP, KOWWINlogP, XLOGP2, XLOGP3), aqueous solubility data (logS), electronic descriptor - polar surface area (PSA), constitutional parameter - molecular weight (Mw), geometric descriptor - volume value (Vol), acidity descriptor (pKa) were calculated using different software packages. The relationships between computed molecular descriptors and literature-obtained oral bioavailability data were firstly investigated using simple linear regression analysis showing relatively poor correlations with R 2 &amp; 0.6. In continuation, multiple linear regression was applied to achieve higher correlation between calcium channel blockers’ oral bioavailability and their molecular properties, on the first place lipophilicity and one additional, molecular descriptor. The best correlations were established between calcium channel blockers’ oral bioavailability and their lipophilicity data (milogP or KOWWINlogP) with application of acidity descriptor as additional independent variable (R 2 = 0.783 and R 2 = 0.826). Application of computed molecular descriptors in evaluating drugs bioavailability was checked on three additional, fourth generation CCBs, cilnidipine, lacidipine, lercandipine.
PB  - Bulgarian Academy of Sciences
T2  - Bulgarian Chemical Communications
T1  - In silico investigation of the relation between calcium channel blockers’ molecular descriptors and oral bioavailability data
VL  - 51
IS  - 1
SP  - 60
EP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3285
ER  - 
@article{
author = "Odović, Jadranka",
year = "2019",
abstract = "Calcium channel blockers are commonly prescribed antihypertensive drugs. In this study, nine calcium channel blockers (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem) were investigated to evaluate the relationship between their molecular properties and oral bioavailability data collected from relevant literature. Several molecular descriptors of calcium channel blockers: lipophilicity descriptors, different logP values (AlogPs, AClogP, AB/logP, milogP, AlogP, MlogP, KOWWINlogP, XLOGP2, XLOGP3), aqueous solubility data (logS), electronic descriptor - polar surface area (PSA), constitutional parameter - molecular weight (Mw), geometric descriptor - volume value (Vol), acidity descriptor (pKa) were calculated using different software packages. The relationships between computed molecular descriptors and literature-obtained oral bioavailability data were firstly investigated using simple linear regression analysis showing relatively poor correlations with R 2 &amp; 0.6. In continuation, multiple linear regression was applied to achieve higher correlation between calcium channel blockers’ oral bioavailability and their molecular properties, on the first place lipophilicity and one additional, molecular descriptor. The best correlations were established between calcium channel blockers’ oral bioavailability and their lipophilicity data (milogP or KOWWINlogP) with application of acidity descriptor as additional independent variable (R 2 = 0.783 and R 2 = 0.826). Application of computed molecular descriptors in evaluating drugs bioavailability was checked on three additional, fourth generation CCBs, cilnidipine, lacidipine, lercandipine.",
publisher = "Bulgarian Academy of Sciences",
journal = "Bulgarian Chemical Communications",
title = "In silico investigation of the relation between calcium channel blockers’ molecular descriptors and oral bioavailability data",
volume = "51",
number = "1",
pages = "60-65",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3285"
}
Odović, J.. (2019). In silico investigation of the relation between calcium channel blockers’ molecular descriptors and oral bioavailability data. in Bulgarian Chemical Communications
Bulgarian Academy of Sciences., 51(1), 60-65.
https://hdl.handle.net/21.15107/rcub_farfar_3285
Odović J. In silico investigation of the relation between calcium channel blockers’ molecular descriptors and oral bioavailability data. in Bulgarian Chemical Communications. 2019;51(1):60-65.
https://hdl.handle.net/21.15107/rcub_farfar_3285 .
Odović, Jadranka, "In silico investigation of the relation between calcium channel blockers’ molecular descriptors and oral bioavailability data" in Bulgarian Chemical Communications, 51, no. 1 (2019):60-65,
https://hdl.handle.net/21.15107/rcub_farfar_3285 .

A 10% Lactobionic acid-containing moisturizer reduces skin surface pH without irritation—An in vivo/in vitro study

Tasić-Kostov, Marija; Lukić, Milica; Savić, Snežana

(Blackwell Publishing Ltd, 2019)

TY  - JOUR
AU  - Tasić-Kostov, Marija
AU  - Lukić, Milica
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3290
AB  - Background/Objectives: Stratum corneum acidification is a newer strategy in management of inflammatory dermatoses; acidifying emollients are normally used for that purpose. However, a decrease in pH of the skin is commonly connected to an increase in irritation. The aim of this study was to investigate whether lactobionic acid (LA), cosmeceutical active and "superacid" belonging to the class of alpha-hydroxy acids (AHAs), could decrease pH of skin surface without irritation. Methods: Safety profile of emulsion based on alkyl polyglucosides (APGs) sugar emulsifiers with 10% LA was evaluated in vitro (acute skin irritation test using cytotoxicity assay), and in vivo in safety study employing measurements of the relevant biophysical human skin parameters upon cessation of 24 hours occlusive treatment: transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin erythema index (EI). The effect on the pH of human skin surface was investigated by pH measurements prior and 1 hour after application of the emulsion with 10% LA. Results: The pH of the skin was significantly reduced after application of LA-containing emulsion. The results for in vitro skin irritation potential assessment were in line with the in vivo safety study, indicating a satisfactory safety profile of both APG-based emulsion vehicle per se and emulsion with 10% LA. Conclusion: Lactobionic acid (10%) in emulsion based on APGs reduces skin surface pH without irritation and skin barrier impairment; it could be proposed as an alternative to low-molecular AHAs in acidifying emollients.
PB  - Blackwell Publishing Ltd
T2  - Journal of Cosmetic Dermatology
T1  - A 10% Lactobionic acid-containing moisturizer reduces skin surface pH without irritation—An in vivo/in vitro study
DO  - 10.1111/jocd.12908
ER  - 
@article{
author = "Tasić-Kostov, Marija and Lukić, Milica and Savić, Snežana",
year = "2019",
abstract = "Background/Objectives: Stratum corneum acidification is a newer strategy in management of inflammatory dermatoses; acidifying emollients are normally used for that purpose. However, a decrease in pH of the skin is commonly connected to an increase in irritation. The aim of this study was to investigate whether lactobionic acid (LA), cosmeceutical active and "superacid" belonging to the class of alpha-hydroxy acids (AHAs), could decrease pH of skin surface without irritation. Methods: Safety profile of emulsion based on alkyl polyglucosides (APGs) sugar emulsifiers with 10% LA was evaluated in vitro (acute skin irritation test using cytotoxicity assay), and in vivo in safety study employing measurements of the relevant biophysical human skin parameters upon cessation of 24 hours occlusive treatment: transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin erythema index (EI). The effect on the pH of human skin surface was investigated by pH measurements prior and 1 hour after application of the emulsion with 10% LA. Results: The pH of the skin was significantly reduced after application of LA-containing emulsion. The results for in vitro skin irritation potential assessment were in line with the in vivo safety study, indicating a satisfactory safety profile of both APG-based emulsion vehicle per se and emulsion with 10% LA. Conclusion: Lactobionic acid (10%) in emulsion based on APGs reduces skin surface pH without irritation and skin barrier impairment; it could be proposed as an alternative to low-molecular AHAs in acidifying emollients.",
publisher = "Blackwell Publishing Ltd",
journal = "Journal of Cosmetic Dermatology",
title = "A 10% Lactobionic acid-containing moisturizer reduces skin surface pH without irritation—An in vivo/in vitro study",
doi = "10.1111/jocd.12908"
}
Tasić-Kostov, M., Lukić, M.,& Savić, S.. (2019). A 10% Lactobionic acid-containing moisturizer reduces skin surface pH without irritation—An in vivo/in vitro study. in Journal of Cosmetic Dermatology
Blackwell Publishing Ltd..
https://doi.org/10.1111/jocd.12908
Tasić-Kostov M, Lukić M, Savić S. A 10% Lactobionic acid-containing moisturizer reduces skin surface pH without irritation—An in vivo/in vitro study. in Journal of Cosmetic Dermatology. 2019;.
doi:10.1111/jocd.12908 .
Tasić-Kostov, Marija, Lukić, Milica, Savić, Snežana, "A 10% Lactobionic acid-containing moisturizer reduces skin surface pH without irritation—An in vivo/in vitro study" in Journal of Cosmetic Dermatology (2019),
https://doi.org/10.1111/jocd.12908 . .
8
11
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8

A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells

Pantelić, Ivana; Ilić, Tanja; Marković, Bojan; Savić, Sanela; Lukić, Milica; Savić, Snežana

(Savez hemijskih inženjera, Beograd, 2018)

TY  - JOUR
AU  - Pantelić, Ivana
AU  - Ilić, Tanja
AU  - Marković, Bojan
AU  - Savić, Sanela
AU  - Lukić, Milica
AU  - Savić, Snežana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3151
AB  - After decades long absence of an official consensus on the most appropriate evaluation method for in vitro skin performance of topical semisolid drugs, United States Pharmacopoeia (USP 39) finally suggested three types of testing equipment; however, all these provide data on drug release using inert synthetic membranes. Considering the need for a readily available membrane that would be more structurally similar to human skin, this paper provides a detailed protocol of a method for drug permeation assessment that uses heat-separated porcine ear epidermis and modified Franz diffusion cells. Phases that were shown to be critical for variability of the results are identified (e.g., membrane preparation), and process parameters optimized. Applicability of the method was tested on four cream samples loaded with aceclofenac as a model drug. Sample compositions were designed in such a way to provide, large "variations (variation of the main stabilizer: natural-origin versus synthetic emulsifier) and relatively, minor" variations (co-solvent variation: none/isopropanol/glycerol). The developed protocol is a straightforward and reliable in vitro test for the evaluation of rate and extent of drug delivery into/through the skin. Moreover, this protocol may be routinely applied even in averagely equipped laboratories during formulation development or preliminary bioequivalence assessment of generic topical semisolids.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells
VL  - 72
IS  - 1
SP  - 47
EP  - 53
DO  - 10.2298/HEMIND170726019P
ER  - 
@article{
author = "Pantelić, Ivana and Ilić, Tanja and Marković, Bojan and Savić, Sanela and Lukić, Milica and Savić, Snežana",
year = "2018",
abstract = "After decades long absence of an official consensus on the most appropriate evaluation method for in vitro skin performance of topical semisolid drugs, United States Pharmacopoeia (USP 39) finally suggested three types of testing equipment; however, all these provide data on drug release using inert synthetic membranes. Considering the need for a readily available membrane that would be more structurally similar to human skin, this paper provides a detailed protocol of a method for drug permeation assessment that uses heat-separated porcine ear epidermis and modified Franz diffusion cells. Phases that were shown to be critical for variability of the results are identified (e.g., membrane preparation), and process parameters optimized. Applicability of the method was tested on four cream samples loaded with aceclofenac as a model drug. Sample compositions were designed in such a way to provide, large "variations (variation of the main stabilizer: natural-origin versus synthetic emulsifier) and relatively, minor" variations (co-solvent variation: none/isopropanol/glycerol). The developed protocol is a straightforward and reliable in vitro test for the evaluation of rate and extent of drug delivery into/through the skin. Moreover, this protocol may be routinely applied even in averagely equipped laboratories during formulation development or preliminary bioequivalence assessment of generic topical semisolids.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells",
volume = "72",
number = "1",
pages = "47-53",
doi = "10.2298/HEMIND170726019P"
}
Pantelić, I., Ilić, T., Marković, B., Savić, S., Lukić, M.,& Savić, S.. (2018). A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 72(1), 47-53.
https://doi.org/10.2298/HEMIND170726019P
Pantelić I, Ilić T, Marković B, Savić S, Lukić M, Savić S. A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells. in Hemijska industrija. 2018;72(1):47-53.
doi:10.2298/HEMIND170726019P .
Pantelić, Ivana, Ilić, Tanja, Marković, Bojan, Savić, Sanela, Lukić, Milica, Savić, Snežana, "A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells" in Hemijska industrija, 72, no. 1 (2018):47-53,
https://doi.org/10.2298/HEMIND170726019P . .
7
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