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 . .

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 . .

TY  - JOUR
AU  - Bubić-Pajić, Nataša
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Ranđelović, Danijela
AU  - Dobričić, Vladimir
AU  - Smitran, Aleksandra
AU  - Cekić, Nebojša
AU  - Čalija, Bojan
AU  - Savić, Snežana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3062
AB  - The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Molecular Liquids
T1  - Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties
VL  - 272
SP  - 746
EP  - 758
DO  - 10.1016/j.molliq.2018.10.002
ER  - 

@article{
author = "Bubić-Pajić, Nataša and Nikolić, Ines and Mitsou, Evgenia and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Ranđelović, Danijela and Dobričić, Vladimir and Smitran, Aleksandra and Cekić, Nebojša and Čalija, Bojan and Savić, Snežana",
year = "2018",
abstract = "The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Molecular Liquids",
title = "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties",
volume = "272",
pages = "746-758",
doi = "10.1016/j.molliq.2018.10.002"
}

Bubić-Pajić, N., Nikolić, I., Mitsou, E., Papadimitriou, V., Xenakis, A., Ranđelović, D., Dobričić, V., Smitran, A., Cekić, N., Čalija, B.,& Savić, S.. (2018). Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids
Elsevier Science BV, Amsterdam., 272, 746-758.
https://doi.org/10.1016/j.molliq.2018.10.002

Bubić-Pajić N, Nikolić I, Mitsou E, Papadimitriou V, Xenakis A, Ranđelović D, Dobričić V, Smitran A, Cekić N, Čalija B, Savić S. Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids. 2018;272:746-758.
doi:10.1016/j.molliq.2018.10.002 .

Bubić-Pajić, Nataša, Nikolić, Ines, Mitsou, Evgenia, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Ranđelović, Danijela, Dobričić, Vladimir, Smitran, Aleksandra, Cekić, Nebojša, Čalija, Bojan, Savić, Snežana, "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties" in Journal of Molecular Liquids, 272 (2018):746-758,
https://doi.org/10.1016/j.molliq.2018.10.002 . .

TY  - JOUR
AU  - Savić, Vedrana
AU  - Todosijević, Marija N.
AU  - Ilić, Tanja
AU  - Lukić, Milica
AU  - Mitsou, Evgenia
AU  - Papadimitriou, Vassiliki
AU  - Avramiotis, Spyridon
AU  - Marković, Bojan
AU  - Cekić, Nebojša
AU  - Savić, Snežana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2823
AB  - In order to improve skin penetration of tacrolimus we aimed to develop potentially non-irritant, lecithin-based microemulsions containing ethanol, isopropanol and/or propylene glycol as cosurfactants, varying caprylic/capric triglycerides and propylene glycol monocaprylate as oil phase. The influence of excipients on the size of microemulsion region in pseudo-ternary phase diagrams and their ability to form different types of microemulsions was evaluated. The comprehensive physicochemical characterization of microemulsions and the evaluation of their structure was performed, while the localization of tacrolimus in microemulsions was further investigated using electron paramagnetic resonance spectroscopy. Moreover, stability studies proved no change in tacrolimus content during one year of storage at room temperature. In addition, in vivo skin performance indicated no skin irritation potential of blank microemulsions, whereas in vitro release testing using Franz diffusion cells showed superior release rate of tacrolimus from microemulsions (0.98 +/- 0.10 and 0.92 +/- 0.11 mu g/cm(2)/h for two bicontinuous and 1.00 +/- 0.24 mu g/cm(2)/h for oil-in-water microemulsion) compared to referent Protopic ointment (0.15 +/- 0.08 mu g/cm(2)/h). Furthermore, ex vivo penetration assessed through porcine ear skin using tape stripping, confirmed superiority of two microemulsions related to the reference, implying developed microemulsions as promising carriers for dermal delivery of tacrolimus.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances
VL  - 529
IS  - 1-2
SP  - 491
EP  - 505
DO  - 10.1016/j.ijpharm.2017.07.036
ER  - 

@article{
author = "Savić, Vedrana and Todosijević, Marija N. and Ilić, Tanja and Lukić, Milica and Mitsou, Evgenia and Papadimitriou, Vassiliki and Avramiotis, Spyridon and Marković, Bojan and Cekić, Nebojša and Savić, Snežana",
year = "2017",
abstract = "In order to improve skin penetration of tacrolimus we aimed to develop potentially non-irritant, lecithin-based microemulsions containing ethanol, isopropanol and/or propylene glycol as cosurfactants, varying caprylic/capric triglycerides and propylene glycol monocaprylate as oil phase. The influence of excipients on the size of microemulsion region in pseudo-ternary phase diagrams and their ability to form different types of microemulsions was evaluated. The comprehensive physicochemical characterization of microemulsions and the evaluation of their structure was performed, while the localization of tacrolimus in microemulsions was further investigated using electron paramagnetic resonance spectroscopy. Moreover, stability studies proved no change in tacrolimus content during one year of storage at room temperature. In addition, in vivo skin performance indicated no skin irritation potential of blank microemulsions, whereas in vitro release testing using Franz diffusion cells showed superior release rate of tacrolimus from microemulsions (0.98 +/- 0.10 and 0.92 +/- 0.11 mu g/cm(2)/h for two bicontinuous and 1.00 +/- 0.24 mu g/cm(2)/h for oil-in-water microemulsion) compared to referent Protopic ointment (0.15 +/- 0.08 mu g/cm(2)/h). Furthermore, ex vivo penetration assessed through porcine ear skin using tape stripping, confirmed superiority of two microemulsions related to the reference, implying developed microemulsions as promising carriers for dermal delivery of tacrolimus.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances",
volume = "529",
number = "1-2",
pages = "491-505",
doi = "10.1016/j.ijpharm.2017.07.036"
}

Savić, V., Todosijević, M. N., Ilić, T., Lukić, M., Mitsou, E., Papadimitriou, V., Avramiotis, S., Marković, B., Cekić, N.,& Savić, S.. (2017). Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 529(1-2), 491-505.
https://doi.org/10.1016/j.ijpharm.2017.07.036

Savić V, Todosijević MN, Ilić T, Lukić M, Mitsou E, Papadimitriou V, Avramiotis S, Marković B, Cekić N, Savić S. Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances. in International Journal of Pharmaceutics. 2017;529(1-2):491-505.
doi:10.1016/j.ijpharm.2017.07.036 .

Savić, Vedrana, Todosijević, Marija N., Ilić, Tanja, Lukić, Milica, Mitsou, Evgenia, Papadimitriou, Vassiliki, Avramiotis, Spyridon, Marković, Bojan, Cekić, Nebojša, Savić, Snežana, "Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances" in International Journal of Pharmaceutics, 529, no. 1-2 (2017):491-505,
https://doi.org/10.1016/j.ijpharm.2017.07.036 . .