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Publications

Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica

Heck, Rouven; Lukić, Milica; Savić, Snežana; Daniels, Rolf; Lunter, Dominique

(Elsevier Science BV, Amsterdam, 2017)

TY  - JOUR
AU  - Heck, Rouven
AU  - Lukić, Milica
AU  - Savić, Snežana
AU  - Daniels, Rolf
AU  - Lunter, Dominique
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2806
AB  - Aim: The purpose of this study was to evaluate skin permeation and penetration of nonivamide which has been formulated in novel film-forming formulations (FFFs). These formulations aim to prolong the availability of capsaicinoids which are used in long-term treatment of chronic pruritus. Methods: An oily solution of nonivamide was loaded into porous silica particles which then were suspended in an aqueous dispersion of a sustained release polymer. Permeation and penetration experiments were performed ex vivo with postauricular porcine skin using modified Franz diffusion cells. The penetrated drug amount was assessed ex vivo by skin surface biopsy followed by cryo-sectioning. Furthermore, in vivo skin irritation experiments were performed to compare the potential skin irritation caused by the FFFs to conventionally used semi-solid formulations. Results: Permeation rates of nonivamide from FFF through the skin are comparable to that from clinically used immediate release formulations. This elucidates the therapeutic safety profile of the novel FFF. Penetration studies confirmed the prolonged drug availability at the site of action. FFFs were found not to irritate the skin of healthy volunteers. Conclusion: FFFs with sustained nonivamide penetration represent safe and easy-to-use formulations. They therefore may improve the treatment of chronic pruritus with capsaicinoids by enhancing patient compliance through a sustained release regime.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica
VL  - 106
SP  - 34
EP  - 40
DO  - 10.1016/j.ejps.2017.05.045
ER  - 
@article{
author = "Heck, Rouven and Lukić, Milica and Savić, Snežana and Daniels, Rolf and Lunter, Dominique",
year = "2017",
abstract = "Aim: The purpose of this study was to evaluate skin permeation and penetration of nonivamide which has been formulated in novel film-forming formulations (FFFs). These formulations aim to prolong the availability of capsaicinoids which are used in long-term treatment of chronic pruritus. Methods: An oily solution of nonivamide was loaded into porous silica particles which then were suspended in an aqueous dispersion of a sustained release polymer. Permeation and penetration experiments were performed ex vivo with postauricular porcine skin using modified Franz diffusion cells. The penetrated drug amount was assessed ex vivo by skin surface biopsy followed by cryo-sectioning. Furthermore, in vivo skin irritation experiments were performed to compare the potential skin irritation caused by the FFFs to conventionally used semi-solid formulations. Results: Permeation rates of nonivamide from FFF through the skin are comparable to that from clinically used immediate release formulations. This elucidates the therapeutic safety profile of the novel FFF. Penetration studies confirmed the prolonged drug availability at the site of action. FFFs were found not to irritate the skin of healthy volunteers. Conclusion: FFFs with sustained nonivamide penetration represent safe and easy-to-use formulations. They therefore may improve the treatment of chronic pruritus with capsaicinoids by enhancing patient compliance through a sustained release regime.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica",
volume = "106",
pages = "34-40",
doi = "10.1016/j.ejps.2017.05.045"
}
Heck, R., Lukić, M., Savić, S., Daniels, R.,& Lunter, D.. (2017). Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 106, 34-40.
https://doi.org/10.1016/j.ejps.2017.05.045
Heck R, Lukić M, Savić S, Daniels R, Lunter D. Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica. in European Journal of Pharmaceutical Sciences. 2017;106:34-40.
doi:10.1016/j.ejps.2017.05.045 .
Heck, Rouven, Lukić, Milica, Savić, Snežana, Daniels, Rolf, Lunter, Dominique, "Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica" in European Journal of Pharmaceutical Sciences, 106 (2017):34-40,
https://doi.org/10.1016/j.ejps.2017.05.045 . .
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Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks

Golubović, Jelena; Birkemeyer, Claudia; Protić, Ana; Otašević, Biljana; Zečević, Mira

(Elsevier Science BV, Amsterdam, 2016)

TY  - JOUR
AU  - Golubović, Jelena
AU  - Birkemeyer, Claudia
AU  - Protić, Ana
AU  - Otašević, Biljana
AU  - Zečević, Mira
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2541
AB  - Quantitative structure-property relationship (QSPR) methods are based on the hypothesis that changes in the molecular structure are reflected in changes in the observed property of the molecule. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. For the first time a quantitative structure-response relationship in electrospray ionization mass spectrometry (ESI-MS) by means of artificial neural networks (ANN) on the group of angiotensin II receptor antagonists - sartans has been established. The investigated descriptors correspond to different properties of the analytes: polarity (logP), ionizability (pKa), surface area (solvent excluded volume) and number of proton acceptors. The influence of the instrumental parameters: methanol content in mobile phase, mobile phase pH and flow rate was also examined. Best performance showed a multilayer perceptron network with the architecture 6-3-3-1, trained with backpropagation algorithm. It showed high prediction ability on the previously unseen (test) data set with a coefficient of determination of 0.994. High prediction ability of the model would enable prediction of ESI-MS responsiveness under different conditions. This is particularly important in the method development phase. Also, prediction of responsiveness can be important in case of gradient-elution LC-MS and LC-MS/MS methods in which instrumental conditions are varied during time. Polarity, chargeability and surface area all appeared to be crucial for electrospray ionization whereby signal intensity appeared to be the result of a simultaneous influence of the molecular descriptors and their interactions. Percentage of organic phase in the mobile phase showed a positive, while flow rate showed a negative impact on signal intensity.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks
VL  - 1438
SP  - 123
EP  - 132
DO  - 10.1016/j.chroma.2016.02.021
ER  - 
@article{
author = "Golubović, Jelena and Birkemeyer, Claudia and Protić, Ana and Otašević, Biljana and Zečević, Mira",
year = "2016",
abstract = "Quantitative structure-property relationship (QSPR) methods are based on the hypothesis that changes in the molecular structure are reflected in changes in the observed property of the molecule. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. For the first time a quantitative structure-response relationship in electrospray ionization mass spectrometry (ESI-MS) by means of artificial neural networks (ANN) on the group of angiotensin II receptor antagonists - sartans has been established. The investigated descriptors correspond to different properties of the analytes: polarity (logP), ionizability (pKa), surface area (solvent excluded volume) and number of proton acceptors. The influence of the instrumental parameters: methanol content in mobile phase, mobile phase pH and flow rate was also examined. Best performance showed a multilayer perceptron network with the architecture 6-3-3-1, trained with backpropagation algorithm. It showed high prediction ability on the previously unseen (test) data set with a coefficient of determination of 0.994. High prediction ability of the model would enable prediction of ESI-MS responsiveness under different conditions. This is particularly important in the method development phase. Also, prediction of responsiveness can be important in case of gradient-elution LC-MS and LC-MS/MS methods in which instrumental conditions are varied during time. Polarity, chargeability and surface area all appeared to be crucial for electrospray ionization whereby signal intensity appeared to be the result of a simultaneous influence of the molecular descriptors and their interactions. Percentage of organic phase in the mobile phase showed a positive, while flow rate showed a negative impact on signal intensity.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks",
volume = "1438",
pages = "123-132",
doi = "10.1016/j.chroma.2016.02.021"
}
Golubović, J., Birkemeyer, C., Protić, A., Otašević, B.,& Zečević, M.. (2016). Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1438, 123-132.
https://doi.org/10.1016/j.chroma.2016.02.021
Golubović J, Birkemeyer C, Protić A, Otašević B, Zečević M. Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks. in Journal of Chromatography A. 2016;1438:123-132.
doi:10.1016/j.chroma.2016.02.021 .
Golubović, Jelena, Birkemeyer, Claudia, Protić, Ana, Otašević, Biljana, Zečević, Mira, "Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks" in Journal of Chromatography A, 1438 (2016):123-132,
https://doi.org/10.1016/j.chroma.2016.02.021 . .
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45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity

Stevanović, Magdalena; Filipović, Nenad; Đurđević, Jelena; Lukić, Miodrag; Milenković, Marina; Boccaccini, Aldo

(Elsevier Science BV, Amsterdam, 2015)

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Filipović, Nenad
AU  - Đurđević, Jelena
AU  - Lukić, Miodrag
AU  - Milenković, Marina
AU  - Boccaccini, Aldo
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2427
AB  - In the bone tissue engineering field, there is a growing interest in the application of bioactive glass scaffolds (45S5Bioglass (R)) due to their bone bonding ability, osteoconductivity and osteoinductivity. However, such scaffolds still lack some of the required functionalities to enable the successful formation of new bone, e.g. effective antibacterial properties. A large number of studies suggest that selenium (Se) has significant role in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Selenium nanoparticles (SeNp) have also been reported to possess antibacterial as well as antiviral activities. In this investigation, uniform, stable, amorphous SeNp have been synthesized and additionally immobilized within spherical PLGA particles (PLGA/SeNp). These particles were used to coat bioactive glass-based scaffolds synthesized by the foam replica method. Samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy. (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). SeNp, 45S5Bioglass (R)/SeNp and 45S5Bioglass (R)/PLGA/SeNp showed a considerable antibacterial activity against Gram positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, one of the main causative agents of orthopedic infections. The functionalized Se-coated bioactive glass scaffolds represent a new family of bioactive, antibacterial scaffolds for bone tissue engineering applications.
PB  - Elsevier Science BV, Amsterdam
T2  - Colloids and Surfaces B: Biointerfaces
T1  - 45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity
VL  - 132
SP  - 208
EP  - 215
DO  - 10.1016/j.colsurfb.2015.05.024
ER  - 
@article{
author = "Stevanović, Magdalena and Filipović, Nenad and Đurđević, Jelena and Lukić, Miodrag and Milenković, Marina and Boccaccini, Aldo",
year = "2015",
abstract = "In the bone tissue engineering field, there is a growing interest in the application of bioactive glass scaffolds (45S5Bioglass (R)) due to their bone bonding ability, osteoconductivity and osteoinductivity. However, such scaffolds still lack some of the required functionalities to enable the successful formation of new bone, e.g. effective antibacterial properties. A large number of studies suggest that selenium (Se) has significant role in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Selenium nanoparticles (SeNp) have also been reported to possess antibacterial as well as antiviral activities. In this investigation, uniform, stable, amorphous SeNp have been synthesized and additionally immobilized within spherical PLGA particles (PLGA/SeNp). These particles were used to coat bioactive glass-based scaffolds synthesized by the foam replica method. Samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy. (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). SeNp, 45S5Bioglass (R)/SeNp and 45S5Bioglass (R)/PLGA/SeNp showed a considerable antibacterial activity against Gram positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, one of the main causative agents of orthopedic infections. The functionalized Se-coated bioactive glass scaffolds represent a new family of bioactive, antibacterial scaffolds for bone tissue engineering applications.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Colloids and Surfaces B: Biointerfaces",
title = "45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity",
volume = "132",
pages = "208-215",
doi = "10.1016/j.colsurfb.2015.05.024"
}
Stevanović, M., Filipović, N., Đurđević, J., Lukić, M., Milenković, M.,& Boccaccini, A.. (2015). 45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity. in Colloids and Surfaces B: Biointerfaces
Elsevier Science BV, Amsterdam., 132, 208-215.
https://doi.org/10.1016/j.colsurfb.2015.05.024
Stevanović M, Filipović N, Đurđević J, Lukić M, Milenković M, Boccaccini A. 45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity. in Colloids and Surfaces B: Biointerfaces. 2015;132:208-215.
doi:10.1016/j.colsurfb.2015.05.024 .
Stevanović, Magdalena, Filipović, Nenad, Đurđević, Jelena, Lukić, Miodrag, Milenković, Marina, Boccaccini, Aldo, "45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity" in Colloids and Surfaces B: Biointerfaces, 132 (2015):208-215,
https://doi.org/10.1016/j.colsurfb.2015.05.024 . .
1
79
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75

Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification

Cvijić, Sandra; Parojčić, Jelena; Langguth, Peter

(Elsevier Science BV, Amsterdam, 2014)

TY  - JOUR
AU  - Cvijić, Sandra
AU  - Parojčić, Jelena
AU  - Langguth, Peter
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2210
AB  - Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence of food is one of the key factors limiting oral absorption of drugs with limited permeability and absorption restricted to the upper parts of the intestine, while having negligible effect on pharmacokinetic profile of drugs with pH- and site-independent absorption. Dissolution medium pH 4.6 with the addition of hydroxypropyl methylcellulose was suggested to simulate postprandial gastric conditions for drugs whose solubility under these conditions is not the limiting factor for drug absorption. In addition, drug formulation was found to be an interfering factor in relation to the impact of medium viscosity on the rate and extent of drug absorption.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification
VL  - 61
SP  - 40
EP  - 53
DO  - 10.1016/j.ejps.2014.04.008
ER  - 
@article{
author = "Cvijić, Sandra and Parojčić, Jelena and Langguth, Peter",
year = "2014",
abstract = "Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence of food is one of the key factors limiting oral absorption of drugs with limited permeability and absorption restricted to the upper parts of the intestine, while having negligible effect on pharmacokinetic profile of drugs with pH- and site-independent absorption. Dissolution medium pH 4.6 with the addition of hydroxypropyl methylcellulose was suggested to simulate postprandial gastric conditions for drugs whose solubility under these conditions is not the limiting factor for drug absorption. In addition, drug formulation was found to be an interfering factor in relation to the impact of medium viscosity on the rate and extent of drug absorption.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification",
volume = "61",
pages = "40-53",
doi = "10.1016/j.ejps.2014.04.008"
}
Cvijić, S., Parojčić, J.,& Langguth, P.. (2014). Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 61, 40-53.
https://doi.org/10.1016/j.ejps.2014.04.008
Cvijić S, Parojčić J, Langguth P. Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification. in European Journal of Pharmaceutical Sciences. 2014;61:40-53.
doi:10.1016/j.ejps.2014.04.008 .
Cvijić, Sandra, Parojčić, Jelena, Langguth, Peter, "Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification" in European Journal of Pharmaceutical Sciences, 61 (2014):40-53,
https://doi.org/10.1016/j.ejps.2014.04.008 . .
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Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation

Kovačević, Anđelka; Mueller, Rainer H.; Savić, Snežana; Vuleta, Gordana; Keck, Cornelia M.

(Elsevier Science BV, Amsterdam, 2014)

TY  - JOUR
AU  - Kovačević, Anđelka
AU  - Mueller, Rainer H.
AU  - Savić, Snežana
AU  - Vuleta, Gordana
AU  - Keck, Cornelia M.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2189
AB  - Polyhydroxy surfactants are nonionic ethylene oxide free stabilizers known for their complimentary dermatological properties and favorable environmental profile. The aim of this study was to develop solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants varying in the chemical structure and to investigate the influence of the surfactants on the characteristics of the particles. Particles were produced by hot high pressure homogenization and the physico-chemical properties, e.g. contact angle, particle size, size distribution, zeta potential and crystallinity were determined. Results showed that the chemical structure of the surfactants influences the contact angle, particle size and crystallinity. Furthermore, the low surfactants concentration used (1% (w/w)) allowed the formation of the particles with a mean size below 200 nm, polydispersity index lower than 0.1 and sufficient physical stability for at least 6 months. As postulated by the zeta potential analysis stabilization ability of the surfactants was attributed to the superposition of electrostatic and steric effect which complement each other. All SLN formulations consisted of the same lipid matrix, but were found to possess different crystallinity indices. These differences are obviously created by the differences in the chemical structure of the surfactants. Therefore, the polyhydroxy surfactants investigated in this study can be judged to be novel suitable stabilizers for the formulation of well-skin tolerable SLN. The use of specific chemical structures of the surfactants can be used for the production of "tailor-made" SLN in the future.
PB  - Elsevier Science BV, Amsterdam
T2  - Colloids and Surfaces A: Physicochemical and Engineering Aspects
T1  - Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation
VL  - 444
SP  - 15
EP  - 25
DO  - 10.1016/j.colsurfa.2013.12.023
ER  - 
@article{
author = "Kovačević, Anđelka and Mueller, Rainer H. and Savić, Snežana and Vuleta, Gordana and Keck, Cornelia M.",
year = "2014",
abstract = "Polyhydroxy surfactants are nonionic ethylene oxide free stabilizers known for their complimentary dermatological properties and favorable environmental profile. The aim of this study was to develop solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants varying in the chemical structure and to investigate the influence of the surfactants on the characteristics of the particles. Particles were produced by hot high pressure homogenization and the physico-chemical properties, e.g. contact angle, particle size, size distribution, zeta potential and crystallinity were determined. Results showed that the chemical structure of the surfactants influences the contact angle, particle size and crystallinity. Furthermore, the low surfactants concentration used (1% (w/w)) allowed the formation of the particles with a mean size below 200 nm, polydispersity index lower than 0.1 and sufficient physical stability for at least 6 months. As postulated by the zeta potential analysis stabilization ability of the surfactants was attributed to the superposition of electrostatic and steric effect which complement each other. All SLN formulations consisted of the same lipid matrix, but were found to possess different crystallinity indices. These differences are obviously created by the differences in the chemical structure of the surfactants. Therefore, the polyhydroxy surfactants investigated in this study can be judged to be novel suitable stabilizers for the formulation of well-skin tolerable SLN. The use of specific chemical structures of the surfactants can be used for the production of "tailor-made" SLN in the future.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Colloids and Surfaces A: Physicochemical and Engineering Aspects",
title = "Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation",
volume = "444",
pages = "15-25",
doi = "10.1016/j.colsurfa.2013.12.023"
}
Kovačević, A., Mueller, R. H., Savić, S., Vuleta, G.,& Keck, C. M.. (2014). Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation. in Colloids and Surfaces A: Physicochemical and Engineering Aspects
Elsevier Science BV, Amsterdam., 444, 15-25.
https://doi.org/10.1016/j.colsurfa.2013.12.023
Kovačević A, Mueller RH, Savić S, Vuleta G, Keck CM. Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation. in Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2014;444:15-25.
doi:10.1016/j.colsurfa.2013.12.023 .
Kovačević, Anđelka, Mueller, Rainer H., Savić, Snežana, Vuleta, Gordana, Keck, Cornelia M., "Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation" in Colloids and Surfaces A: Physicochemical and Engineering Aspects, 444 (2014):15-25,
https://doi.org/10.1016/j.colsurfa.2013.12.023 . .
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Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants

Keck, Cornelia M.; Kovacević, Anđelka; Mueller, Rainer H.; Savić, Snežana; Vuleta, Gordana; Milić, Jela

(Elsevier Science BV, Amsterdam, 2014)

TY  - JOUR
AU  - Keck, Cornelia M.
AU  - Kovacević, Anđelka
AU  - Mueller, Rainer H.
AU  - Savić, Snežana
AU  - Vuleta, Gordana
AU  - Milić, Jela
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2078
AB  - Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150 nm and 175 nm and a narrow size distribution. The zeta potential in water was similar to -50 mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5 degrees C, 25 degrees C and 40 degrees C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilized with classical surfactants, e.g., Polysorbate, APG stabilized SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e., to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but also SLN with different sizes and crystallinity can be obtained. An optimized selection of these stabilizers might therefore enable the production of lipid nanoparticles with "tailor-made" properties.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants
VL  - 474
IS  - 1-2
SP  - 33
EP  - 41
DO  - 10.1016/j.ijpharm.2014.08.008
ER  - 
@article{
author = "Keck, Cornelia M. and Kovacević, Anđelka and Mueller, Rainer H. and Savić, Snežana and Vuleta, Gordana and Milić, Jela",
year = "2014",
abstract = "Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150 nm and 175 nm and a narrow size distribution. The zeta potential in water was similar to -50 mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5 degrees C, 25 degrees C and 40 degrees C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilized with classical surfactants, e.g., Polysorbate, APG stabilized SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e., to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but also SLN with different sizes and crystallinity can be obtained. An optimized selection of these stabilizers might therefore enable the production of lipid nanoparticles with "tailor-made" properties.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants",
volume = "474",
number = "1-2",
pages = "33-41",
doi = "10.1016/j.ijpharm.2014.08.008"
}
Keck, C. M., Kovacević, A., Mueller, R. H., Savić, S., Vuleta, G.,& Milić, J.. (2014). Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 474(1-2), 33-41.
https://doi.org/10.1016/j.ijpharm.2014.08.008
Keck CM, Kovacević A, Mueller RH, Savić S, Vuleta G, Milić J. Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants. in International Journal of Pharmaceutics. 2014;474(1-2):33-41.
doi:10.1016/j.ijpharm.2014.08.008 .
Keck, Cornelia M., Kovacević, Anđelka, Mueller, Rainer H., Savić, Snežana, Vuleta, Gordana, Milić, Jela, "Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants" in International Journal of Pharmaceutics, 474, no. 1-2 (2014):33-41,
https://doi.org/10.1016/j.ijpharm.2014.08.008 . .
57
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57

Stability evaluation of temoporfin-loaded liposomal gels for topical application

Dragičević-Curić, Nina; Winter, Sven; Krajišnik, Danina; Stupar, Mirjana; Milić, Jela; Graefe, Susanna; Fahr, Alfred

(Taylor & Francis Ltd, Abingdon, 2010)

TY  - JOUR
AU  - Dragičević-Curić, Nina
AU  - Winter, Sven
AU  - Krajišnik, Danina
AU  - Stupar, Mirjana
AU  - Milić, Jela
AU  - Graefe, Susanna
AU  - Fahr, Alfred
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1386
AB  - Temoporfin (mTHPC) is a potent second-generation synthetic photosensitizer. Topical delivery of mTHPC is of great interest for the photodynamic therapy of psoriasis and superficial skin cancer lesions. The aim of this study was to evaluate the stability of hydrophilic gels containing mTHPC-loaded liposomes. Two different mTHPC-loaded liposome dispersions, composed of 15 % (w/w) nonhydrogenated soybean lecithin of different phosphatidylcholine content, were prepared and incorporated (2:1 w/w) into hydrogels of different carbomer concentrations (1.5, 2.25, and 3%; w/w). Obtained liposomal hydrogels, containing 0.15% (w/w) mTHPC, 10% (w/w) phospholipids, and 0, 0.5, or 1% (w/w) carbomer, were analyzed for flow properties, liposome particle size, and polydispersity index (PDI), pH value, and mTHPC content after their preparation and at predetermined time intervals during 6 months of storage at 4 and 23 degrees C. All hydrogels showed, during the whole period of investigation, adequate characteristics for topical application (i.e., they revealed shear-thinning plastic flow behavior). Rheological parameters, particle size, and PDI of liposomes in hydrogels, mTHPC content, and pH value did not show remarkable changes during the storage of gels, which could make them unacceptable for topical use. The obtained results indicated physical and chemical stability of liposomal gels containing mTHPC during 6 months of storage at both temperatures.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Journal of Liposome Research
T1  - Stability evaluation of temoporfin-loaded liposomal gels for topical application
VL  - 20
IS  - 1
SP  - 38
EP  - 48
DO  - 10.3109/08982100903030263
ER  - 
@article{
author = "Dragičević-Curić, Nina and Winter, Sven and Krajišnik, Danina and Stupar, Mirjana and Milić, Jela and Graefe, Susanna and Fahr, Alfred",
year = "2010",
abstract = "Temoporfin (mTHPC) is a potent second-generation synthetic photosensitizer. Topical delivery of mTHPC is of great interest for the photodynamic therapy of psoriasis and superficial skin cancer lesions. The aim of this study was to evaluate the stability of hydrophilic gels containing mTHPC-loaded liposomes. Two different mTHPC-loaded liposome dispersions, composed of 15 % (w/w) nonhydrogenated soybean lecithin of different phosphatidylcholine content, were prepared and incorporated (2:1 w/w) into hydrogels of different carbomer concentrations (1.5, 2.25, and 3%; w/w). Obtained liposomal hydrogels, containing 0.15% (w/w) mTHPC, 10% (w/w) phospholipids, and 0, 0.5, or 1% (w/w) carbomer, were analyzed for flow properties, liposome particle size, and polydispersity index (PDI), pH value, and mTHPC content after their preparation and at predetermined time intervals during 6 months of storage at 4 and 23 degrees C. All hydrogels showed, during the whole period of investigation, adequate characteristics for topical application (i.e., they revealed shear-thinning plastic flow behavior). Rheological parameters, particle size, and PDI of liposomes in hydrogels, mTHPC content, and pH value did not show remarkable changes during the storage of gels, which could make them unacceptable for topical use. The obtained results indicated physical and chemical stability of liposomal gels containing mTHPC during 6 months of storage at both temperatures.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Journal of Liposome Research",
title = "Stability evaluation of temoporfin-loaded liposomal gels for topical application",
volume = "20",
number = "1",
pages = "38-48",
doi = "10.3109/08982100903030263"
}
Dragičević-Curić, N., Winter, S., Krajišnik, D., Stupar, M., Milić, J., Graefe, S.,& Fahr, A.. (2010). Stability evaluation of temoporfin-loaded liposomal gels for topical application. in Journal of Liposome Research
Taylor & Francis Ltd, Abingdon., 20(1), 38-48.
https://doi.org/10.3109/08982100903030263
Dragičević-Curić N, Winter S, Krajišnik D, Stupar M, Milić J, Graefe S, Fahr A. Stability evaluation of temoporfin-loaded liposomal gels for topical application. in Journal of Liposome Research. 2010;20(1):38-48.
doi:10.3109/08982100903030263 .
Dragičević-Curić, Nina, Winter, Sven, Krajišnik, Danina, Stupar, Mirjana, Milić, Jela, Graefe, Susanna, Fahr, Alfred, "Stability evaluation of temoporfin-loaded liposomal gels for topical application" in Journal of Liposome Research, 20, no. 1 (2010):38-48,
https://doi.org/10.3109/08982100903030263 . .
29
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34

Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity

Vezmar, Sandra; Bode, Udo; Jaehde, Ulrich

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2009)

TY  - JOUR
AU  - Vezmar, Sandra
AU  - Bode, Udo
AU  - Jaehde, Ulrich
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1167
AB  - Intrathecal and/or high-dose intravenous administration of methotrexate (MTX) in the treatment of malignancies such as acute lymphoblastic leukaemia (ALL) has been associated with cases of mild to severe neurotoxicity. The pathogenic mechanism of neurotoxicity is not clear possibly MTX-associated biochemical alterations of the folate and methyl-transfer metabolic pathways play an important role. We report a case of an adult patient treated for ALL relapse with signs of chronic leukoencephalopathy associated with MTX administration. In order to assess alterations in the folate and methyl-transfer pathway we determined 5-methyltetrahydrofolate (5-methyl-THF), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the cerebrospinal fluid (CSF) of the patient. Three CSF samples were obtained by lumbar punction within a four-month period. Concentrations of the metabolites were measured using validated bioanalytical methods based on HPLC with UV and fluorescence detection. The results showed two-fold lower 5-methyl-THF levels (29.3-31.8 nmol/L) in all obtained samples compared to reference values. SAM concentrations were even more than five-fold lower in two samples (5-34.2 nmol/L). SAH concentrations were in the range 7.5-14.3 nmol/L. Our patient had pronounced alterations in the folate and methyl-transfer pathway which indicate that MTX-associated biochemical alterations of these pathways may play an important role in the development of leukoencephalopathy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity
VL  - 28
IS  - 1
SP  - 11
EP  - 15
DO  - 10.2478/v10011-008-0027-y
ER  - 
@article{
author = "Vezmar, Sandra and Bode, Udo and Jaehde, Ulrich",
year = "2009",
abstract = "Intrathecal and/or high-dose intravenous administration of methotrexate (MTX) in the treatment of malignancies such as acute lymphoblastic leukaemia (ALL) has been associated with cases of mild to severe neurotoxicity. The pathogenic mechanism of neurotoxicity is not clear possibly MTX-associated biochemical alterations of the folate and methyl-transfer metabolic pathways play an important role. We report a case of an adult patient treated for ALL relapse with signs of chronic leukoencephalopathy associated with MTX administration. In order to assess alterations in the folate and methyl-transfer pathway we determined 5-methyltetrahydrofolate (5-methyl-THF), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the cerebrospinal fluid (CSF) of the patient. Three CSF samples were obtained by lumbar punction within a four-month period. Concentrations of the metabolites were measured using validated bioanalytical methods based on HPLC with UV and fluorescence detection. The results showed two-fold lower 5-methyl-THF levels (29.3-31.8 nmol/L) in all obtained samples compared to reference values. SAM concentrations were even more than five-fold lower in two samples (5-34.2 nmol/L). SAH concentrations were in the range 7.5-14.3 nmol/L. Our patient had pronounced alterations in the folate and methyl-transfer pathway which indicate that MTX-associated biochemical alterations of these pathways may play an important role in the development of leukoencephalopathy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity",
volume = "28",
number = "1",
pages = "11-15",
doi = "10.2478/v10011-008-0027-y"
}
Vezmar, S., Bode, U.,& Jaehde, U.. (2009). Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 28(1), 11-15.
https://doi.org/10.2478/v10011-008-0027-y
Vezmar S, Bode U, Jaehde U. Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity. in Journal of Medical Biochemistry. 2009;28(1):11-15.
doi:10.2478/v10011-008-0027-y .
Vezmar, Sandra, Bode, Udo, Jaehde, Ulrich, "Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity" in Journal of Medical Biochemistry, 28, no. 1 (2009):11-15,
https://doi.org/10.2478/v10011-008-0027-y . .
2
2
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