TY  - JOUR
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, Jovana
AU  - Marković, Bojan
AU  - Vujić, Zorica
AU  - Lazović, Saša
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5549
AB  - Abstract: The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis.
PB  - Pleiades Publishing
T2  - Journal of Analytical Chemistry
T1  - Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds
VL  - 79
IS  - 1
SP  - 95
EP  - 104
DO  - 10.1134/S1061934824010076
ER  - 

@article{
author = "Obradović, Darija and Savić, Jelena and Joksimović, Jovana and Marković, Bojan and Vujić, Zorica and Lazović, Saša",
year = "2024",
abstract = "Abstract: The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis.",
publisher = "Pleiades Publishing",
journal = "Journal of Analytical Chemistry",
title = "Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds",
volume = "79",
number = "1",
pages = "95-104",
doi = "10.1134/S1061934824010076"
}

Obradović, D., Savić, J., Joksimović, J., Marković, B., Vujić, Z.,& Lazović, S.. (2024). Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds. in Journal of Analytical Chemistry
Pleiades Publishing., 79(1), 95-104.
https://doi.org/10.1134/S1061934824010076

Obradović D, Savić J, Joksimović J, Marković B, Vujić Z, Lazović S. Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds. in Journal of Analytical Chemistry. 2024;79(1):95-104.
doi:10.1134/S1061934824010076 .

Obradović, Darija, Savić, Jelena, Joksimović, Jovana, Marković, Bojan, Vujić, Zorica, Lazović, Saša, "Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds" in Journal of Analytical Chemistry, 79, no. 1 (2024):95-104,
https://doi.org/10.1134/S1061934824010076 . .

TY  - CONF
AU  - Đoković, Jelena
AU  - Marković, Bojan
AU  - Sharmin, Dishary
AU  - Cook, James M.
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5049
AB  - Introduction Nanopharmaceuticals offer a good method to avoid some of the difficulties that novel drug candidates confront. They can be tailored to adjust their water solubility, half-life, biodistribution, and govern the release of the integrated medication. Because of the excipients utilized, lipid nanocarriers (liposomes, nanoemulsions (NEs), nanoparticles) have been used to increase brain targeting (1,2). The investigated compound (GL-II-73) - (4R)-8-ethynyl-6-(2-fluorophenyl)-N,N,4-trimethyl-4H-benzo[f]imidazo[1,5-a] [1,4]diazepine-3-carboxamide is imidazobenzodiazepine (IBZD) ligand that acts as positive allosteric modulator on α-GABAA receptors and was shown to possess combined antidepressant and pro-cognitive effects, making it a promising candidate for further research (3). This work aims to investigate the physicochemical features of GL-II-73 to pick the best parenteral nanodelivery system for prospective research to assess its parameters. Мaterials and methods The saturation solubility of GL-II-73 was determined by adding it in excess to various oils (medium chain triglycerides, soybean, castor, and fish oil) to assess the oil solubility for the substance and select the optimal oil phase composition capable of incorporating the highest concentration of the GL-II-73. It was necessary to test the substance's solubility in buffers of various pH values to determine whether it has pH-dependent solubility. This investigation was carried out by incubating GL-II-73 and studied mediums on vortex for 24 hours and centrifuging to isolate supernatants from which the GL-II-73 concentration was evaluated using the LC-MS/MS method. The measurements were taken three times. In addition, after a 24-hour equilibration interval and determination of the GL-II-73 concentration, the log P value was obtained in an octanol/water system. Based on these findings, preliminary GL-II-73 (NE) was prepared using the high pressure homogenization method. In brief, the oil and aqueous phases were prepared separately and heated to 50 ˚C. They were then pre-mixed at the rotor stator homogenizer before being homogenized for 10 discontinuous cycles at 800 bar on the high pressure homogenizer. After diluting the sample in 1:500, v/v, ultra-purified water, the resulting formulations were characterized in terms of droplet size using the dynamic light scattering (DLS) technique on a Zetasizer Nano ZS90 (Malvern Instruments Ltd., Worcestershire, U.K.). On the same equipment, the NE's zeta potential (ZP) was measured. In addition, the pH and conductivity of the samples were examined. The ultrafiltration technique was used to evaluate the encapsulation efficacy (EE) by depositing 2 ml of the material in Amicon Ultra-4; NMWL 10 kDa filter units and centrifuging at 4500 rcf for 90 minutes. The EE was computed as %EE = ((A formulation A filtrate)/A formulation) 100, where A formulation represents the compound content in the formulation and A filtrate represents the filtrate, which was diluted in methanol and analyzed for Gl-II-73 content using the LC-MS/MS technique. During the one-month storage period, these conditions were monitored. Results and discussion Table 1 shows the solubility of GL-II-73 in the oils and buffers tested. The relatively good oil solubility, together with the log P value of 2.09, suggested that NEs could be promising carriers for GL-II-73. The highest oil solubility was detected in medium chain triglycerides, making them the oil phase of choice for future formulation development. Based on the solubility in 0.1 M HCl and phosphate buffer pH 7.4, it is possible to deduce that GL-II-73 has pH dependent solubility, with increased solubility observed as pH decreases, most likely due to the presence of ionizable functional groups and multiple H-bond acceptors. This suggested that the best EE would most likely be obtained by increasing the pH of the aqueous phase and keeping the chemical entrapped in the NE droplets. Solubility in organic solvents revealed that methanol is the best solvent for GL-II-73, as expected given its greater polarity index compared to isopropanol, which is why it was chosen for future characterization. Based on the solubility study, NE of the following composition was prepared: oil phase - medium chain tryglicerides (20%, w/w), soybean lecithin (2%, w/w), buthylhidroxytoluen (0.05%, w/w) and aqueous phase polysorbate 80 (2%, w/w), glycerol (2.25%, w/w), sodium oleate (0.03%, w/w), GL-II-73 (0.2%, w/w) and highly purified water to 100. The values of physicochemical parameters (Z-ave, PDI, ZP, pH, conductivity, drug content and encapsulation efficacy), measured both initially and after one month of storage, indicate suitability for parenteral administration. Conclusion Preliminary studies suggested that NEs are good prospective carriers for GL-II-73, but further research is needed for stability optimization.
PB  - Macedonian Pharmaceutical Association
PB  - Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy
C3  - 14th Central European Symposium on Pharmaceutical Technology, 28th - 30th September, Ohrid, N. Macedonia
T1  - Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5049
ER  - 

@conference{
author = "Đoković, Jelena and Marković, Bojan and Sharmin, Dishary and Cook, James M. and Savić, Miroslav and Savić, Snežana",
year = "2023",
abstract = "Introduction Nanopharmaceuticals offer a good method to avoid some of the difficulties that novel drug candidates confront. They can be tailored to adjust their water solubility, half-life, biodistribution, and govern the release of the integrated medication. Because of the excipients utilized, lipid nanocarriers (liposomes, nanoemulsions (NEs), nanoparticles) have been used to increase brain targeting (1,2). The investigated compound (GL-II-73) - (4R)-8-ethynyl-6-(2-fluorophenyl)-N,N,4-trimethyl-4H-benzo[f]imidazo[1,5-a] [1,4]diazepine-3-carboxamide is imidazobenzodiazepine (IBZD) ligand that acts as positive allosteric modulator on α-GABAA receptors and was shown to possess combined antidepressant and pro-cognitive effects, making it a promising candidate for further research (3). This work aims to investigate the physicochemical features of GL-II-73 to pick the best parenteral nanodelivery system for prospective research to assess its parameters. Мaterials and methods The saturation solubility of GL-II-73 was determined by adding it in excess to various oils (medium chain triglycerides, soybean, castor, and fish oil) to assess the oil solubility for the substance and select the optimal oil phase composition capable of incorporating the highest concentration of the GL-II-73. It was necessary to test the substance's solubility in buffers of various pH values to determine whether it has pH-dependent solubility. This investigation was carried out by incubating GL-II-73 and studied mediums on vortex for 24 hours and centrifuging to isolate supernatants from which the GL-II-73 concentration was evaluated using the LC-MS/MS method. The measurements were taken three times. In addition, after a 24-hour equilibration interval and determination of the GL-II-73 concentration, the log P value was obtained in an octanol/water system. Based on these findings, preliminary GL-II-73 (NE) was prepared using the high pressure homogenization method. In brief, the oil and aqueous phases were prepared separately and heated to 50 ˚C. They were then pre-mixed at the rotor stator homogenizer before being homogenized for 10 discontinuous cycles at 800 bar on the high pressure homogenizer. After diluting the sample in 1:500, v/v, ultra-purified water, the resulting formulations were characterized in terms of droplet size using the dynamic light scattering (DLS) technique on a Zetasizer Nano ZS90 (Malvern Instruments Ltd., Worcestershire, U.K.). On the same equipment, the NE's zeta potential (ZP) was measured. In addition, the pH and conductivity of the samples were examined. The ultrafiltration technique was used to evaluate the encapsulation efficacy (EE) by depositing 2 ml of the material in Amicon Ultra-4; NMWL 10 kDa filter units and centrifuging at 4500 rcf for 90 minutes. The EE was computed as %EE = ((A formulation A filtrate)/A formulation) 100, where A formulation represents the compound content in the formulation and A filtrate represents the filtrate, which was diluted in methanol and analyzed for Gl-II-73 content using the LC-MS/MS technique. During the one-month storage period, these conditions were monitored. Results and discussion Table 1 shows the solubility of GL-II-73 in the oils and buffers tested. The relatively good oil solubility, together with the log P value of 2.09, suggested that NEs could be promising carriers for GL-II-73. The highest oil solubility was detected in medium chain triglycerides, making them the oil phase of choice for future formulation development. Based on the solubility in 0.1 M HCl and phosphate buffer pH 7.4, it is possible to deduce that GL-II-73 has pH dependent solubility, with increased solubility observed as pH decreases, most likely due to the presence of ionizable functional groups and multiple H-bond acceptors. This suggested that the best EE would most likely be obtained by increasing the pH of the aqueous phase and keeping the chemical entrapped in the NE droplets. Solubility in organic solvents revealed that methanol is the best solvent for GL-II-73, as expected given its greater polarity index compared to isopropanol, which is why it was chosen for future characterization. Based on the solubility study, NE of the following composition was prepared: oil phase - medium chain tryglicerides (20%, w/w), soybean lecithin (2%, w/w), buthylhidroxytoluen (0.05%, w/w) and aqueous phase polysorbate 80 (2%, w/w), glycerol (2.25%, w/w), sodium oleate (0.03%, w/w), GL-II-73 (0.2%, w/w) and highly purified water to 100. The values of physicochemical parameters (Z-ave, PDI, ZP, pH, conductivity, drug content and encapsulation efficacy), measured both initially and after one month of storage, indicate suitability for parenteral administration. Conclusion Preliminary studies suggested that NEs are good prospective carriers for GL-II-73, but further research is needed for stability optimization.",
publisher = "Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy",
journal = "14th Central European Symposium on Pharmaceutical Technology, 28th - 30th September, Ohrid, N. Macedonia",
title = "Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5049"
}

Đoković, J., Marković, B., Sharmin, D., Cook, J. M., Savić, M.,& Savić, S.. (2023). Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73. in 14th Central European Symposium on Pharmaceutical Technology, 28th - 30th September, Ohrid, N. Macedonia
Macedonian Pharmaceutical Association..
https://hdl.handle.net/21.15107/rcub_farfar_5049

Đoković J, Marković B, Sharmin D, Cook JM, Savić M, Savić S. Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73. in 14th Central European Symposium on Pharmaceutical Technology, 28th - 30th September, Ohrid, N. Macedonia. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5049 .

Đoković, Jelena, Marković, Bojan, Sharmin, Dishary, Cook, James M., Savić, Miroslav, Savić, Snežana, "Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73" in 14th Central European Symposium on Pharmaceutical Technology, 28th - 30th September, Ohrid, N. Macedonia (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5049 .

TY  - CONF
AU  - Đoković, Jelena
AU  - Marković, Bojan
AU  - Sharmin, Dishary
AU  - Cook, James M.
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5050
AB  - Nanopharmaceuticals offer a good option to avoid
some of the difficulties that novel drug candidates
confront. They can be tailored to adjust their water
solubility, half-life, biodistribution, and govern the release
of the integrated medication. Because of the excipients
utilized, lipid nanocarriers (liposomes, nanoemulsions
(NEs), nanoparticles) have been used to increase brain
targeting (Bisso et al., 2020; Ilić et al., 2023).
The investigated compound (GL-II-73) - (4R)-8-
ethynyl-6-(2-fluorophenyl)-N,N,4-trimethyl-4H-
benzo[f]imidazo[1,5-a] [1,4]diazepine-3-carboxamide is
imidazobenzodiazepine (IBZD) ligand that acts as positive
allosteric modulator on α-GABAA receptors and was
shown to possess combined antidepressant and pro-
cognitive effects, making it a promising candidate for
further research (Prevot et al., 2019).
This work aims to investigate the physicochemical
features of GL-II-73 to pick the best parenteral
nanodelivery system for prospective research to assess its
parameters.
PB  - Macedonian Pharmaceutical Association
PB  - Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy
C3  - Macedonian Pharmaceutical Bulletin
T1  - Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73
VL  - 69
IS  - Suppl 1
SP  - 53
EP  - 54
DO  - 10.33320/maced.pharm.bull.2023.69.03.026
ER  - 

@conference{
author = "Đoković, Jelena and Marković, Bojan and Sharmin, Dishary and Cook, James M. and Savić, Miroslav and Savić, Snežana",
year = "2023",
abstract = "Nanopharmaceuticals offer a good option to avoid
some of the difficulties that novel drug candidates
confront. They can be tailored to adjust their water
solubility, half-life, biodistribution, and govern the release
of the integrated medication. Because of the excipients
utilized, lipid nanocarriers (liposomes, nanoemulsions
(NEs), nanoparticles) have been used to increase brain
targeting (Bisso et al., 2020; Ilić et al., 2023).
The investigated compound (GL-II-73) - (4R)-8-
ethynyl-6-(2-fluorophenyl)-N,N,4-trimethyl-4H-
benzo[f]imidazo[1,5-a] [1,4]diazepine-3-carboxamide is
imidazobenzodiazepine (IBZD) ligand that acts as positive
allosteric modulator on α-GABAA receptors and was
shown to possess combined antidepressant and pro-
cognitive effects, making it a promising candidate for
further research (Prevot et al., 2019).
This work aims to investigate the physicochemical
features of GL-II-73 to pick the best parenteral
nanodelivery system for prospective research to assess its
parameters.",
publisher = "Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy",
journal = "Macedonian Pharmaceutical Bulletin",
title = "Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73",
volume = "69",
number = "Suppl 1",
pages = "53-54",
doi = "10.33320/maced.pharm.bull.2023.69.03.026"
}

Đoković, J., Marković, B., Sharmin, D., Cook, J. M., Savić, M.,& Savić, S.. (2023). Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 69(Suppl 1), 53-54.
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.026

Đoković J, Marković B, Sharmin D, Cook JM, Savić M, Savić S. Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73. in Macedonian Pharmaceutical Bulletin. 2023;69(Suppl 1):53-54.
doi:10.33320/maced.pharm.bull.2023.69.03.026 .

Đoković, Jelena, Marković, Bojan, Sharmin, Dishary, Cook, James M., Savić, Miroslav, Savić, Snežana, "Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73" in Macedonian Pharmaceutical Bulletin, 69, no. Suppl 1 (2023):53-54,
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.026 . .

TY  - CONF
AU  - Đoković, Jelena
AU  - Marković, Bojan
AU  - Sharmin, Dishary
AU  - Cook, James M.
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4999
AB  - Searching for the best way to incorporate the proprietary compound GL-II -73 into the nanoemulsion carrier for prospective parenteral application
Jelena Đoković1, Bojan Marković2, Dishary Sharmin3, James M Cook3, Miroslav Savić4, Snežana Savić1
1University of pharmacy - Faculty of pharmacy, Department of pharmaceutical technology and cosmetology, 11221 Belgrade, Serbia
2University of pharmacy - Faculty of pharmacy, Department of pharmaceutical chemistry, 11221 Belgrade, Serbia
3Department of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA
4University of pharmacy - Faculty of pharmacy, Department of pharmacology, 11221 Belgrade, Serbia
The maximum amount of drug that can be incorporated into lipid nanoemulsions (NE) is usually judged by their solubility in the internal phase of the formulation. This can lead to various problems, such as precipitation of the drug after processing the formulation or, depending on the preparation technique used, the use of a large amount of the drug. To this end, it is useful to consider other drug loading methods, especially in the early stages of formulation development. In this study, we aimed to find the best way to achieve the highest loading of GL-II -73 in NEs for future parenteral applications for in vivo animal studies. This ligand acts as a positive allosteric modulator at α-GABAA receptors with combined antidepressant and cognition enhancing effects. NEs were prepared using the high pressure homogenization technique, a standard technique for parenteral NE preparation. The oil phase (medium-chain triglycerides, soy lecithin, and butylated hydroxytoluene) and the aqueous phase (glycerol, polysorbate 80, and 0.01 M phosphate buffer, pH 8) were separately heated to 50 ˚C and mixed until all components were dissolved. The aqueous phase was added to the oil phase and processed first on a rotor-stator homogenizer at 11000 rpm for 1 minute and then on a high-pressure homogenizer at 800 bar for 10 cycles. This resulted in a droplet size of 117.1 ± 1.5 nm, a PDI of 0.060 ± 0.008, a zeta potential of - 43.3 ± 1.3 mV, a pH of 7.89 ± 0.02, and a conductivity of 1061.67 ± 5.51 S/cm, indicating initial suitability for parenteral use. Using the empirical method for drug loading, we were able to dissolve GL-II -73 in the oil phase and achieve a drug concentration of 1.5 mg/ml in NE. For our experimental setup, this required the use of 120 mg of GL-II -73 per experiment. For the passive drug loading procedure, we incubated 1 ml of the placebo NE in the eppendorf tube (in duplicate) with the excess drug (approximately 10 mg per tube) for 72 h. The drug was then added to the eppendorf tube. The excess of the undissolved drug was removed after centrifugation. The drug content in the supernatant was 3.10 ± 0.25 mg/ml, indicating above-average loading of the drug and possibly suggesting localization of the drug in the droplet-stabilising layer, but this needs to be further demonstrated. This approach could contribute to more rational formulation development in the selection of formulation factors.
Acknowledgments
This research was funded by the Science Fund of the Republic of Serbia, GRANT No 7749108, Neuroimmune aspects of mood, anxiety and cognitive effects of leads/drug candidates acting at GABAA and/or sigma-2 receptors: In vitro/in vivo delineation by nano- and hiPSC-based platform - NanoCellEmоCog.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Searching for the best way to incorporate the proprietary compound GL-II -73 into the nanoemulsion carrier for prospective parenteral application
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4999
ER  - 

@conference{
author = "Đoković, Jelena and Marković, Bojan and Sharmin, Dishary and Cook, James M. and Savić, Miroslav and Savić, Snežana",
year = "2023",
abstract = "Searching for the best way to incorporate the proprietary compound GL-II -73 into the nanoemulsion carrier for prospective parenteral application
Jelena Đoković1, Bojan Marković2, Dishary Sharmin3, James M Cook3, Miroslav Savić4, Snežana Savić1
1University of pharmacy - Faculty of pharmacy, Department of pharmaceutical technology and cosmetology, 11221 Belgrade, Serbia
2University of pharmacy - Faculty of pharmacy, Department of pharmaceutical chemistry, 11221 Belgrade, Serbia
3Department of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA
4University of pharmacy - Faculty of pharmacy, Department of pharmacology, 11221 Belgrade, Serbia
The maximum amount of drug that can be incorporated into lipid nanoemulsions (NE) is usually judged by their solubility in the internal phase of the formulation. This can lead to various problems, such as precipitation of the drug after processing the formulation or, depending on the preparation technique used, the use of a large amount of the drug. To this end, it is useful to consider other drug loading methods, especially in the early stages of formulation development. In this study, we aimed to find the best way to achieve the highest loading of GL-II -73 in NEs for future parenteral applications for in vivo animal studies. This ligand acts as a positive allosteric modulator at α-GABAA receptors with combined antidepressant and cognition enhancing effects. NEs were prepared using the high pressure homogenization technique, a standard technique for parenteral NE preparation. The oil phase (medium-chain triglycerides, soy lecithin, and butylated hydroxytoluene) and the aqueous phase (glycerol, polysorbate 80, and 0.01 M phosphate buffer, pH 8) were separately heated to 50 ˚C and mixed until all components were dissolved. The aqueous phase was added to the oil phase and processed first on a rotor-stator homogenizer at 11000 rpm for 1 minute and then on a high-pressure homogenizer at 800 bar for 10 cycles. This resulted in a droplet size of 117.1 ± 1.5 nm, a PDI of 0.060 ± 0.008, a zeta potential of - 43.3 ± 1.3 mV, a pH of 7.89 ± 0.02, and a conductivity of 1061.67 ± 5.51 S/cm, indicating initial suitability for parenteral use. Using the empirical method for drug loading, we were able to dissolve GL-II -73 in the oil phase and achieve a drug concentration of 1.5 mg/ml in NE. For our experimental setup, this required the use of 120 mg of GL-II -73 per experiment. For the passive drug loading procedure, we incubated 1 ml of the placebo NE in the eppendorf tube (in duplicate) with the excess drug (approximately 10 mg per tube) for 72 h. The drug was then added to the eppendorf tube. The excess of the undissolved drug was removed after centrifugation. The drug content in the supernatant was 3.10 ± 0.25 mg/ml, indicating above-average loading of the drug and possibly suggesting localization of the drug in the droplet-stabilising layer, but this needs to be further demonstrated. This approach could contribute to more rational formulation development in the selection of formulation factors.
Acknowledgments
This research was funded by the Science Fund of the Republic of Serbia, GRANT No 7749108, Neuroimmune aspects of mood, anxiety and cognitive effects of leads/drug candidates acting at GABAA and/or sigma-2 receptors: In vitro/in vivo delineation by nano- and hiPSC-based platform - NanoCellEmоCog.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Searching for the best way to incorporate the proprietary compound GL-II -73 into the nanoemulsion carrier for prospective parenteral application",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4999"
}

Đoković, J., Marković, B., Sharmin, D., Cook, J. M., Savić, M.,& Savić, S.. (2023). Searching for the best way to incorporate the proprietary compound GL-II -73 into the nanoemulsion carrier for prospective parenteral application. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists..
https://hdl.handle.net/21.15107/rcub_farfar_4999

Đoković J, Marković B, Sharmin D, Cook JM, Savić M, Savić S. Searching for the best way to incorporate the proprietary compound GL-II -73 into the nanoemulsion carrier for prospective parenteral application. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_4999 .

Đoković, Jelena, Marković, Bojan, Sharmin, Dishary, Cook, James M., Savić, Miroslav, Savić, Snežana, "Searching for the best way to incorporate the proprietary compound GL-II -73 into the nanoemulsion carrier for prospective parenteral application" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023),
https://hdl.handle.net/21.15107/rcub_farfar_4999 .

TY  - JOUR
AU  - Ivković, Branka
AU  - Milutinović, Ivana
AU  - Čudina, Olivera
AU  - Marković, Bojan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4086
AB  - Gentamicin sulfate is a potent broad spectrum aminoglycoside antibiotic which is used against Gram- positive and Gram-negative bacteria. A simple, isocratic HPLC method for separation, identification and determination of gentamicin and parabens (methylparaben and propylparaben) was developed and validated. To our knowledge there is no report about simultaneous determination of those three ana- lytes in pharmaceutical products. The optimum chromatographic conditions were achieved on CN column with a mobile phase consisting of 0.15% triethylamine in 10 mM KH 2 PO4 aqueous solution (final pH 3.0 adjusted with H 3 PO 4 ) and methanol in the ratio 70:30 (v/v), providing selective quan- tification of analytes within 5 min. The method was successfully validated according to ICH guidelines acceptance criteria in terms of selectivity, linearity, accuracy, precision and robustness. The linearity of the method was proved in defined concentrations ranges for gentamicin (0.32–1.04 mg mL1 ), meth- ylparaben (0.0072–0.0234 mg mL1 ) and propylparaben (0.0008–0.0026 mg mL1 ). Relative standard deviations calculated for all analytes in precision testing were <2% (analysis repeatability) and <3% (intermediate precision). Recovery values were between 98.87% and 101.67%. Chromatographic pa- rameters are not significantly influenced by small variations of column temperature, pH and molarity of KH2 PO 4 . Finally, the method was successfully applied for quantitative determination of gentamicin and parabens in commercially available solution for injection. Proposed HPLC method is found to be promising in terms of simplicity, analysis times and non-use of derivatization and ion-pair agents.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben
VL  - 35
IS  - 1
SP  - 81
EP  - 87
DO  - 10.1556/1326.2022.00999
ER  - 

@article{
author = "Ivković, Branka and Milutinović, Ivana and Čudina, Olivera and Marković, Bojan",
year = "2023",
abstract = "Gentamicin sulfate is a potent broad spectrum aminoglycoside antibiotic which is used against Gram- positive and Gram-negative bacteria. A simple, isocratic HPLC method for separation, identification and determination of gentamicin and parabens (methylparaben and propylparaben) was developed and validated. To our knowledge there is no report about simultaneous determination of those three ana- lytes in pharmaceutical products. The optimum chromatographic conditions were achieved on CN column with a mobile phase consisting of 0.15% triethylamine in 10 mM KH 2 PO4 aqueous solution (final pH 3.0 adjusted with H 3 PO 4 ) and methanol in the ratio 70:30 (v/v), providing selective quan- tification of analytes within 5 min. The method was successfully validated according to ICH guidelines acceptance criteria in terms of selectivity, linearity, accuracy, precision and robustness. The linearity of the method was proved in defined concentrations ranges for gentamicin (0.32–1.04 mg mL1 ), meth- ylparaben (0.0072–0.0234 mg mL1 ) and propylparaben (0.0008–0.0026 mg mL1 ). Relative standard deviations calculated for all analytes in precision testing were <2% (analysis repeatability) and <3% (intermediate precision). Recovery values were between 98.87% and 101.67%. Chromatographic pa- rameters are not significantly influenced by small variations of column temperature, pH and molarity of KH2 PO 4 . Finally, the method was successfully applied for quantitative determination of gentamicin and parabens in commercially available solution for injection. Proposed HPLC method is found to be promising in terms of simplicity, analysis times and non-use of derivatization and ion-pair agents.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben",
volume = "35",
number = "1",
pages = "81-87",
doi = "10.1556/1326.2022.00999"
}

Ivković, B., Milutinović, I., Čudina, O.,& Marković, B.. (2023). A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben. in Acta Chromatographica
Akademiai Kiado ZRt.., 35(1), 81-87.
https://doi.org/10.1556/1326.2022.00999

Ivković B, Milutinović I, Čudina O, Marković B. A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben. in Acta Chromatographica. 2023;35(1):81-87.
doi:10.1556/1326.2022.00999 .

Ivković, Branka, Milutinović, Ivana, Čudina, Olivera, Marković, Bojan, "A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben" in Acta Chromatographica, 35, no. 1 (2023):81-87,
https://doi.org/10.1556/1326.2022.00999 . .

TY  - JOUR
AU  - Vasić, Marija
AU  - Topić, Aleksandra
AU  - Marković, Bojan
AU  - Milinković, Neda
AU  - Dinčić, Evica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4397
AB  - Background: Multiple sclerosis (MS) is characterized by
inflammation, demyelination and axonal degeneration.
Oxidative stress (OS) plays a significant role in the pathogenesis of the disease. The aim of the study was to examine the association between OS and smoking on the MS
development.
Methods: The study included 175 patients with relapsing-
remitting multiple sclerosis (RRMS) (76 males, 99 females)
and 254 healthy subjects (81 males and 173 females).
Oxidative stress biomarkers in serum, Total Antioxidant
Status (TAS) and Total Oxidative Status (TOS) were determined spectrophotometrically. Oxidative Stress Index (OSI)
was calculated as the ratio of TOS and TAS. Urinary 8-oxo-
7,8-dihydro-2’-deoxyguanosine were determined by
HPLC-MS/MS and expressed as 8-oxodG/creatinine.
Results: In females with RRMS were higher TOS, OSI and
8-oxodG/creatinine than in females in control group. The
group of males with RRMS had lower level of TAS than the
males in control group. Higher levels of 8-oxodG/creatinine was obtained in active, passive and former smokers
with RRMS than in control group with the same exposition
to tobacco smoke. Independent predictors of MS are passive smoking, increased OSI and increased levels of urinary
8-oxodG/creatinine.
Conclusions: Our results demonstrate that the OS parameters should be included in the assessment of the risk for MS
development. Due to the more sensitivity to oxidative
stress, females may be at higher risk of MS development.
This data indicates the importance of introducing the
antioxidant therapy as a complementary treatment in
patients with RRMS.
AB  - Uvod: Multipla skleroza (MS) se karakteriše upalom, demijelinizacijom i degeneracijom aksona. Oksidativni stres (OS) igra značajnu ulogu u patogenezi bolesti. Cilj studije je bio da se ispita povezanost OS i pušenja na razvoj MS. Metode: Studija je obuhvatila 175 pacijenata sa relapsnoremitentnom multiplom sklerozom (RRMS) (76 muškaraca, 99 žena) i 254 zdrava ispitanika (81 muškarac i 173 žene). Biomarkeri oksidativnog stresa u serumu, ukupni antioksidativni status (TAS) i ukupni oksidativni status (TOS) su određeni spektrofotometrijski. Indeks oksidativnog stresa (OSI) je izračunat kao odnos TOS i TAS. Urinarni 8-okso7,8-dihidro-2'-deoksiguanozin je određen HPLC-MS/MS i izražen kao 8-oksoG/kreatinin. Rezultati: Kod žena sa RRMS bili su viši TOS, OSI i 8okodG/kreatinin nego kod žena u kontrolnoj grupi. Grupa muškaraca sa RRMS imala je niži nivo TAS od muškaraca u kontrolnoj grupi. Veći nivoi 8-okodG/kreatinina su dobijeni kod aktivnih, pasivnih i bivših pušača sa RRMS nego u kontrolnoj grupi sa istom izloženošću duvanskom dimu. Nezavisni prediktori MS su pasivno pušenje, povećan OSI i povećani nivoi 8-okodG/kreatinina u urinu. Zaključak: Naši rezultati pokazuju da parametre OS treba uključiti u procenu rizika za razvoj MS. Zbog veće osetljivosti na oksidativni stres, žene mogu biti izložene većem riziku od razvoja MS. Ovi podaci ukazuju na značaj uvođenja antioksidativne terapije kao komplementarnog lečenja kod pacijenata sa RRMS.
PB  - Beograd : Društvo medicinskih biohemičara Srbije
T2  - Journal of Medical Biochemistry
T1  - Oxidative stress-related risk of the multiple sclerosis development
T1  - Rizik razvoja multiple skleroze povezan sa oksidativnim stresom
VL  - 42
IS  - 1
SP  - 1
EP  - 8
DO  - 10.5937/jomb0-37546
ER  - 

@article{
author = "Vasić, Marija and Topić, Aleksandra and Marković, Bojan and Milinković, Neda and Dinčić, Evica",
year = "2023",
abstract = "Background: Multiple sclerosis (MS) is characterized by
inflammation, demyelination and axonal degeneration.
Oxidative stress (OS) plays a significant role in the pathogenesis of the disease. The aim of the study was to examine the association between OS and smoking on the MS
development.
Methods: The study included 175 patients with relapsing-
remitting multiple sclerosis (RRMS) (76 males, 99 females)
and 254 healthy subjects (81 males and 173 females).
Oxidative stress biomarkers in serum, Total Antioxidant
Status (TAS) and Total Oxidative Status (TOS) were determined spectrophotometrically. Oxidative Stress Index (OSI)
was calculated as the ratio of TOS and TAS. Urinary 8-oxo-
7,8-dihydro-2’-deoxyguanosine were determined by
HPLC-MS/MS and expressed as 8-oxodG/creatinine.
Results: In females with RRMS were higher TOS, OSI and
8-oxodG/creatinine than in females in control group. The
group of males with RRMS had lower level of TAS than the
males in control group. Higher levels of 8-oxodG/creatinine was obtained in active, passive and former smokers
with RRMS than in control group with the same exposition
to tobacco smoke. Independent predictors of MS are passive smoking, increased OSI and increased levels of urinary
8-oxodG/creatinine.
Conclusions: Our results demonstrate that the OS parameters should be included in the assessment of the risk for MS
development. Due to the more sensitivity to oxidative
stress, females may be at higher risk of MS development.
This data indicates the importance of introducing the
antioxidant therapy as a complementary treatment in
patients with RRMS., Uvod: Multipla skleroza (MS) se karakteriše upalom, demijelinizacijom i degeneracijom aksona. Oksidativni stres (OS) igra značajnu ulogu u patogenezi bolesti. Cilj studije je bio da se ispita povezanost OS i pušenja na razvoj MS. Metode: Studija je obuhvatila 175 pacijenata sa relapsnoremitentnom multiplom sklerozom (RRMS) (76 muškaraca, 99 žena) i 254 zdrava ispitanika (81 muškarac i 173 žene). Biomarkeri oksidativnog stresa u serumu, ukupni antioksidativni status (TAS) i ukupni oksidativni status (TOS) su određeni spektrofotometrijski. Indeks oksidativnog stresa (OSI) je izračunat kao odnos TOS i TAS. Urinarni 8-okso7,8-dihidro-2'-deoksiguanozin je određen HPLC-MS/MS i izražen kao 8-oksoG/kreatinin. Rezultati: Kod žena sa RRMS bili su viši TOS, OSI i 8okodG/kreatinin nego kod žena u kontrolnoj grupi. Grupa muškaraca sa RRMS imala je niži nivo TAS od muškaraca u kontrolnoj grupi. Veći nivoi 8-okodG/kreatinina su dobijeni kod aktivnih, pasivnih i bivših pušača sa RRMS nego u kontrolnoj grupi sa istom izloženošću duvanskom dimu. Nezavisni prediktori MS su pasivno pušenje, povećan OSI i povećani nivoi 8-okodG/kreatinina u urinu. Zaključak: Naši rezultati pokazuju da parametre OS treba uključiti u procenu rizika za razvoj MS. Zbog veće osetljivosti na oksidativni stres, žene mogu biti izložene većem riziku od razvoja MS. Ovi podaci ukazuju na značaj uvođenja antioksidativne terapije kao komplementarnog lečenja kod pacijenata sa RRMS.",
publisher = "Beograd : Društvo medicinskih biohemičara Srbije",
journal = "Journal of Medical Biochemistry",
title = "Oxidative stress-related risk of the multiple sclerosis development, Rizik razvoja multiple skleroze povezan sa oksidativnim stresom",
volume = "42",
number = "1",
pages = "1-8",
doi = "10.5937/jomb0-37546"
}

Vasić, M., Topić, A., Marković, B., Milinković, N.,& Dinčić, E.. (2023). Oxidative stress-related risk of the multiple sclerosis development. in Journal of Medical Biochemistry
Beograd : Društvo medicinskih biohemičara Srbije., 42(1), 1-8.
https://doi.org/10.5937/jomb0-37546

Vasić M, Topić A, Marković B, Milinković N, Dinčić E. Oxidative stress-related risk of the multiple sclerosis development. in Journal of Medical Biochemistry. 2023;42(1):1-8.
doi:10.5937/jomb0-37546 .

Vasić, Marija, Topić, Aleksandra, Marković, Bojan, Milinković, Neda, Dinčić, Evica, "Oxidative stress-related risk of the multiple sclerosis development" in Journal of Medical Biochemistry, 42, no. 1 (2023):1-8,
https://doi.org/10.5937/jomb0-37546 . .

TY  - JOUR
AU  - Ivković, Branka
AU  - Crevar, Milkica
AU  - Cvetanović, Anka
AU  - Ubavkić, Katarina
AU  - Marković, Bojan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4435
AB  - Corticosteroids are anti-inflammatory and immunosuppressant drugs. Topical corticosteroids formulations (ointments, creams, gels) are used in the treatment of different types of dermatitis and urticaria. Considering their therapeutic and whitening effects, they are frequently used for counterfeiting of cosmetic products. Corticosteroids can cause different local and systemic side effects. HPLC method is often chosen for their analysis, because it is selective, sensitive, precise, simple and fast. The aim of this study was optimization and validation of RP-HPLC method with UV detection for determination of trace levels of corticosteroids in ambiphilic creams. This method is used for qualitative and quantitative analysis of evaluated corticosteroids. Mometasone furoate, hydrocortisone acetate, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone dipropionate and triamcinolone acetonide were evaluated. Separation was performed on Inertsil® ODS-3V 250 × 4.6 mm, 5 μm chromatographic column. Mobile phase was mixture of acetonitrile and water 50:50 (v/v) with gradient elution and flow rate 1 mL min-1. Column temperature was held on 40 °C and UV detection was performed at 240 nm. Selectivity, linearity, accuracy, precision and limit of quantification (LOQ) were evaluated. Method is selective because ambiphilic cream base peaks and corticosteroids peaks were not overlapping. Linearity was confirmed since correlation coefficient was 1 for all compounds. Accuracy and precision were evaluated for hydrocortisone acetate and betamethasone dipropionate. Determined Recovery values were in range of 70-130%. Both RSD values (21.46% and 9.59%) were lower than 30%. Method is highly sensitive since LOQ concentrations were in ng mL-1 range. All evaluated parameters of validation were in accordance with regulatory requirements. Validated RP-HPLC method can be used for qualitative and quantitative analysis of selected corticosteroids in ambiphilic creams.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream
VL  - 35
IS  - 1
SP  - 46
EP  - 51
DO  - 10.1556/1326.2021.00998
ER  - 

@article{
author = "Ivković, Branka and Crevar, Milkica and Cvetanović, Anka and Ubavkić, Katarina and Marković, Bojan",
year = "2023",
abstract = "Corticosteroids are anti-inflammatory and immunosuppressant drugs. Topical corticosteroids formulations (ointments, creams, gels) are used in the treatment of different types of dermatitis and urticaria. Considering their therapeutic and whitening effects, they are frequently used for counterfeiting of cosmetic products. Corticosteroids can cause different local and systemic side effects. HPLC method is often chosen for their analysis, because it is selective, sensitive, precise, simple and fast. The aim of this study was optimization and validation of RP-HPLC method with UV detection for determination of trace levels of corticosteroids in ambiphilic creams. This method is used for qualitative and quantitative analysis of evaluated corticosteroids. Mometasone furoate, hydrocortisone acetate, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone dipropionate and triamcinolone acetonide were evaluated. Separation was performed on Inertsil® ODS-3V 250 × 4.6 mm, 5 μm chromatographic column. Mobile phase was mixture of acetonitrile and water 50:50 (v/v) with gradient elution and flow rate 1 mL min-1. Column temperature was held on 40 °C and UV detection was performed at 240 nm. Selectivity, linearity, accuracy, precision and limit of quantification (LOQ) were evaluated. Method is selective because ambiphilic cream base peaks and corticosteroids peaks were not overlapping. Linearity was confirmed since correlation coefficient was 1 for all compounds. Accuracy and precision were evaluated for hydrocortisone acetate and betamethasone dipropionate. Determined Recovery values were in range of 70-130%. Both RSD values (21.46% and 9.59%) were lower than 30%. Method is highly sensitive since LOQ concentrations were in ng mL-1 range. All evaluated parameters of validation were in accordance with regulatory requirements. Validated RP-HPLC method can be used for qualitative and quantitative analysis of selected corticosteroids in ambiphilic creams.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream",
volume = "35",
number = "1",
pages = "46-51",
doi = "10.1556/1326.2021.00998"
}

Ivković, B., Crevar, M., Cvetanović, A., Ubavkić, K.,& Marković, B.. (2023). Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream. in Acta Chromatographica
Akademiai Kiado ZRt.., 35(1), 46-51.
https://doi.org/10.1556/1326.2021.00998

Ivković B, Crevar M, Cvetanović A, Ubavkić K, Marković B. Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream. in Acta Chromatographica. 2023;35(1):46-51.
doi:10.1556/1326.2021.00998 .

Ivković, Branka, Crevar, Milkica, Cvetanović, Anka, Ubavkić, Katarina, Marković, Bojan, "Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream" in Acta Chromatographica, 35, no. 1 (2023):46-51,
https://doi.org/10.1556/1326.2021.00998 . .

Jaćević, V., Dumanović, J., Grujić-Milanović, J., Milovanović, Z., Amidžić, L., Vojinović, N., Nežić, L., Marković, B., Dobričić, V., Milosavljević, P., Nepovimova, E.,& Kuča, K.. (2023). Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-biological interactions
Elsevier B.V.., 383, 110658.
https://doi.org/10.1016/j.cbi.2023.110658

Jaćević V, Dumanović J, Grujić-Milanović J, Milovanović Z, Amidžić L, Vojinović N, Nežić L, Marković B, Dobričić V, Milosavljević P, Nepovimova E, Kuča K. Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-biological interactions. 2023;383:110658.
doi:10.1016/j.cbi.2023.110658 .

Jaćević, Vesna, Dumanović, Jelena, Grujić-Milanović, Jelica, Milovanović, Zoran, Amidžić, Ljiljana, Vojinović, Nataša, Nežić, Lana, Marković, Bojan, Dobričić, Vladimir, Milosavljević, Petar, Nepovimova, Eugenie, Kuča, Kamil, "Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes" in Chemico-biological interactions, 383 (2023):110658,
https://doi.org/10.1016/j.cbi.2023.110658 . .

TY  - CONF
AU  - Čarapić, Marija
AU  - Petković, Miloš
AU  - Marković, Bojan
AU  - Popović-Nikolić, Marija
AU  - Agbaba, Danica
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4684
AB  - Ziprasidone (ZIP) is the second generation antipsychotic drug with unique G-protein-coupled
(GPCR) receptor binding profile. It is a highly lipophilic and unstable compound. Our group
developed and validated the single liquid chromatographic (LC) system for simultaneous
determination of ZIP and its five main impurities (IMPs) and we modelled the Quantitative
Structure Retention Relationship (QSRR) of the additional ten compounds including unknown
detected degradant. One of two proposed structures were confirmed by UPLC-MS/MS study. The
further characterisation of unknown degradant was performed with NMR studies as un versatile
tool for characterisation of each compound and it is presented. Through several experiments which consists of investigation of chemical shitfs in NMR spectra of ZIP degradation products the
structure of unknown degradant was proposed and confirmed as in previous experiments.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
T1  - Characterization of unknown degradant of ziprasidone with NMR spetroscopy
VL  - II
SP  - 601
EP  - 604
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4684
ER  - 

@conference{
author = "Čarapić, Marija and Petković, Miloš and Marković, Bojan and Popović-Nikolić, Marija and Agbaba, Danica and Nikolić, Katarina",
year = "2022",
abstract = "Ziprasidone (ZIP) is the second generation antipsychotic drug with unique G-protein-coupled
(GPCR) receptor binding profile. It is a highly lipophilic and unstable compound. Our group
developed and validated the single liquid chromatographic (LC) system for simultaneous
determination of ZIP and its five main impurities (IMPs) and we modelled the Quantitative
Structure Retention Relationship (QSRR) of the additional ten compounds including unknown
detected degradant. One of two proposed structures were confirmed by UPLC-MS/MS study. The
further characterisation of unknown degradant was performed with NMR studies as un versatile
tool for characterisation of each compound and it is presented. Through several experiments which consists of investigation of chemical shitfs in NMR spectra of ZIP degradation products the
structure of unknown degradant was proposed and confirmed as in previous experiments.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)",
title = "Characterization of unknown degradant of ziprasidone with NMR spetroscopy",
volume = "II",
pages = "601-604",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4684"
}

Čarapić, M., Petković, M., Marković, B., Popović-Nikolić, M., Agbaba, D.,& Nikolić, K.. (2022). Characterization of unknown degradant of ziprasidone with NMR spetroscopy. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
Society of Physical Chemists of Serbia., II, 601-604.
https://hdl.handle.net/21.15107/rcub_farfar_4684

Čarapić M, Petković M, Marković B, Popović-Nikolić M, Agbaba D, Nikolić K. Characterization of unknown degradant of ziprasidone with NMR spetroscopy. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings). 2022;II:601-604.
https://hdl.handle.net/21.15107/rcub_farfar_4684 .

Čarapić, Marija, Petković, Miloš, Marković, Bojan, Popović-Nikolić, Marija, Agbaba, Danica, Nikolić, Katarina, "Characterization of unknown degradant of ziprasidone with NMR spetroscopy" in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings), II (2022):601-604,
https://hdl.handle.net/21.15107/rcub_farfar_4684 .

TY  - JOUR
AU  - Timotijević, Mirjana
AU  - Ilić, Tanja
AU  - Marković, Bojan
AU  - Ranđelović, Danijela
AU  - Cekić, Nebojša
AU  - Nikolić, Ines
AU  - Savić, Snežana
AU  - Pantelić, Ivana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4169
AB  - Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization chal- lenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico- chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit® RS PO and hy- droxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm2 h), and even the pH of the sample with Eudragit® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study
VL  - 23
IS  - 11
DO  - 10.3390/ijms23116013
ER  - 

@article{
author = "Timotijević, Mirjana and Ilić, Tanja and Marković, Bojan and Ranđelović, Danijela and Cekić, Nebojša and Nikolić, Ines and Savić, Snežana and Pantelić, Ivana",
year = "2022",
abstract = "Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization chal- lenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico- chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit® RS PO and hy- droxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm2 h), and even the pH of the sample with Eudragit® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study",
volume = "23",
number = "11",
doi = "10.3390/ijms23116013"
}

Timotijević, M., Ilić, T., Marković, B., Ranđelović, D., Cekić, N., Nikolić, I., Savić, S.,& Pantelić, I.. (2022). Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study. in International Journal of Molecular Sciences
MDPI., 23(11).
https://doi.org/10.3390/ijms23116013

Timotijević M, Ilić T, Marković B, Ranđelović D, Cekić N, Nikolić I, Savić S, Pantelić I. Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study. in International Journal of Molecular Sciences. 2022;23(11).
doi:10.3390/ijms23116013 .

Timotijević, Mirjana, Ilić, Tanja, Marković, Bojan, Ranđelović, Danijela, Cekić, Nebojša, Nikolić, Ines, Savić, Snežana, Pantelić, Ivana, "Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study" in International Journal of Molecular Sciences, 23, no. 11 (2022),
https://doi.org/10.3390/ijms23116013 . .

TY  - JOUR
AU  - Nikolić, Ines
AU  - Simić, Mitar
AU  - Pantelić, Ivana
AU  - Stojanović, Goran
AU  - Antić-Stanković, Jelena
AU  - Marković, Bojan
AU  - Savić, Snežana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4328
AB  - So far, various approaches have been proposed to improve dermal drug delivery. The
use of chemical penetration enhancers has a long history of application, while methods based on
the electrical current (such as iontophoresis) stand out as promising “active” techniques. Aiming to
evaluate the contribution of different approaches to dermal delivery, in this work curcumin-loaded
nanoemulsions with and without monoterpenes (eucalyptol or pinene) as chemical penetration
enhancers, and a custom-made adhesive dermal delivery system based on iontophoresis were
designed and assessed. In an in vivo study applying skin bioengineering techniques, their safety
profile was proven. Three examined iontophoresis protocols, with total skin exposure time of 15 min
(continuous flow for 15 min (15-0); 3 min of continuous flow and 2 min pause (3-2; 5 cycles) and
5 min of continuous flow and 1 min pause (5-1; 3 cycles) were equally efficient in terms of the
total amount of curcumin that penetrated through the superficial skin layers ( in vivo tape stripping)
(Q3-2 = 7.04 ± 3.21 μg/cm2; Q5-1 = 6.66 ± 2.11 μg/cm2; Q15-0 = 6.96 ± 3.21 μg/cm2), significantly
more efficient compared to the referent nanoemulsion and monoterpene-containing nanoemulsions.
Further improvement of an efficient mobile adhesive system for iontophoresis would be a practical
contribution in the field of dermal drug application.
PB  - MDPI
T2  - Pharmaceutics
T1  - Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis
VL  - 14
IS  - 6
DO  - 10.3390/pharmaceutics14061144
ER  - 

@article{
author = "Nikolić, Ines and Simić, Mitar and Pantelić, Ivana and Stojanović, Goran and Antić-Stanković, Jelena and Marković, Bojan and Savić, Snežana",
year = "2022",
abstract = "So far, various approaches have been proposed to improve dermal drug delivery. The
use of chemical penetration enhancers has a long history of application, while methods based on
the electrical current (such as iontophoresis) stand out as promising “active” techniques. Aiming to
evaluate the contribution of different approaches to dermal delivery, in this work curcumin-loaded
nanoemulsions with and without monoterpenes (eucalyptol or pinene) as chemical penetration
enhancers, and a custom-made adhesive dermal delivery system based on iontophoresis were
designed and assessed. In an in vivo study applying skin bioengineering techniques, their safety
profile was proven. Three examined iontophoresis protocols, with total skin exposure time of 15 min
(continuous flow for 15 min (15-0); 3 min of continuous flow and 2 min pause (3-2; 5 cycles) and
5 min of continuous flow and 1 min pause (5-1; 3 cycles) were equally efficient in terms of the
total amount of curcumin that penetrated through the superficial skin layers ( in vivo tape stripping)
(Q3-2 = 7.04 ± 3.21 μg/cm2; Q5-1 = 6.66 ± 2.11 μg/cm2; Q15-0 = 6.96 ± 3.21 μg/cm2), significantly
more efficient compared to the referent nanoemulsion and monoterpene-containing nanoemulsions.
Further improvement of an efficient mobile adhesive system for iontophoresis would be a practical
contribution in the field of dermal drug application.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis",
volume = "14",
number = "6",
doi = "10.3390/pharmaceutics14061144"
}

Nikolić, I., Simić, M., Pantelić, I., Stojanović, G., Antić-Stanković, J., Marković, B.,& Savić, S.. (2022). Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis. in Pharmaceutics
MDPI., 14(6).
https://doi.org/10.3390/pharmaceutics14061144

Nikolić I, Simić M, Pantelić I, Stojanović G, Antić-Stanković J, Marković B, Savić S. Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis. in Pharmaceutics. 2022;14(6).
doi:10.3390/pharmaceutics14061144 .

Nikolić, Ines, Simić, Mitar, Pantelić, Ivana, Stojanović, Goran, Antić-Stanković, Jelena, Marković, Bojan, Savić, Snežana, "Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis" in Pharmaceutics, 14, no. 6 (2022),
https://doi.org/10.3390/pharmaceutics14061144 . .

TY  - JOUR
AU  - Đoković, Jelena
AU  - Demisli, Sotiria
AU  - Savić, Sanela
AU  - Marković, Bojan
AU  - Cekić, Nebojša D.
AU  - Ranđelović, Danijela V.
AU  - Mitrović, Jelena
AU  - Lunter, Dominique Jasmin
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Savić, Snežana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4265
AB  - A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions
PB  - MDPI
T2  - Pharmaceutics
T1  - The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions
VL  - 14
IS  - 8
DO  - 10.3390/pharmaceutics14081666
ER  - 

@article{
author = "Đoković, Jelena and Demisli, Sotiria and Savić, Sanela and Marković, Bojan and Cekić, Nebojša D. and Ranđelović, Danijela V. and Mitrović, Jelena and Lunter, Dominique Jasmin and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Savić, Snežana",
year = "2022",
abstract = "A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions",
volume = "14",
number = "8",
doi = "10.3390/pharmaceutics14081666"
}

Đoković, J., Demisli, S., Savić, S., Marković, B., Cekić, N. D., Ranđelović, D. V., Mitrović, J., Lunter, D. J., Papadimitriou, V., Xenakis, A.,& Savić, S.. (2022). The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions. in Pharmaceutics
MDPI., 14(8).
https://doi.org/10.3390/pharmaceutics14081666

Đoković J, Demisli S, Savić S, Marković B, Cekić ND, Ranđelović DV, Mitrović J, Lunter DJ, Papadimitriou V, Xenakis A, Savić S. The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions. in Pharmaceutics. 2022;14(8).
doi:10.3390/pharmaceutics14081666 .

Đoković, Jelena, Demisli, Sotiria, Savić, Sanela, Marković, Bojan, Cekić, Nebojša D., Ranđelović, Danijela V., Mitrović, Jelena, Lunter, Dominique Jasmin, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Savić, Snežana, "The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions" in Pharmaceutics, 14, no. 8 (2022),
https://doi.org/10.3390/pharmaceutics14081666 . .

TY  - JOUR
AU  - Dabetić, Nevena
AU  - Todorović, Vanja
AU  - Malenović, Anđelija
AU  - Šobajić, Slađana
AU  - Marković, Bojan
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4268
AB  - Winemaking generates large quantities of grape waste consisting of seeds, skin and stalks. Given that grape seeds are a rich source of different bioactive compounds, the main goal of this research was to optimize grape seed phenol extraction using a Box–Behnken design. The following conditions were derived from the optimization process: sample:solvent ratio of 1:10 w/v, extraction time of 30 min and extraction temperature of 50 °C. In addition, a sustainable (green) approach for obtaining extracts was developed by comparing choline chloride:citric acid-ChCit (natural deep eutectic solvent (NADES)) and ethanol extraction methods with respect to phenol profiles and antioxidant activity. This study was conducted on seeds from eight different red grape varieties. Phenolic acids, flavan-3-ols and procyanidins were characterized using HPLC–MS/MS, and the concentration of procyanidin B1 was above 1 mg/g of dry weight in all analyzed samples. The contents of all phenol classes and antioxidant activities were found to not differ significantly between the solvents, but NADES was found to offer valuable advantages. Importantly, ChCit showed a strong affinity toward procyanidins and a strong correlation between antioxidant activity and quantified phenolic compounds.
PB  - MDPI
T2  - Antioxidants
T1  - Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents
VL  - 11
IS  - 8
DO  - 10.3390/antiox11081595
ER  - 

@article{
author = "Dabetić, Nevena and Todorović, Vanja and Malenović, Anđelija and Šobajić, Slađana and Marković, Bojan",
year = "2022",
abstract = "Winemaking generates large quantities of grape waste consisting of seeds, skin and stalks. Given that grape seeds are a rich source of different bioactive compounds, the main goal of this research was to optimize grape seed phenol extraction using a Box–Behnken design. The following conditions were derived from the optimization process: sample:solvent ratio of 1:10 w/v, extraction time of 30 min and extraction temperature of 50 °C. In addition, a sustainable (green) approach for obtaining extracts was developed by comparing choline chloride:citric acid-ChCit (natural deep eutectic solvent (NADES)) and ethanol extraction methods with respect to phenol profiles and antioxidant activity. This study was conducted on seeds from eight different red grape varieties. Phenolic acids, flavan-3-ols and procyanidins were characterized using HPLC–MS/MS, and the concentration of procyanidin B1 was above 1 mg/g of dry weight in all analyzed samples. The contents of all phenol classes and antioxidant activities were found to not differ significantly between the solvents, but NADES was found to offer valuable advantages. Importantly, ChCit showed a strong affinity toward procyanidins and a strong correlation between antioxidant activity and quantified phenolic compounds.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents",
volume = "11",
number = "8",
doi = "10.3390/antiox11081595"
}

Dabetić, N., Todorović, V., Malenović, A., Šobajić, S.,& Marković, B.. (2022). Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents. in Antioxidants
MDPI., 11(8).
https://doi.org/10.3390/antiox11081595

Dabetić N, Todorović V, Malenović A, Šobajić S, Marković B. Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents. in Antioxidants. 2022;11(8).
doi:10.3390/antiox11081595 .

Dabetić, Nevena, Todorović, Vanja, Malenović, Anđelija, Šobajić, Slađana, Marković, Bojan, "Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents" in Antioxidants, 11, no. 8 (2022),
https://doi.org/10.3390/antiox11081595 . .

TY  - JOUR
AU  - Koravović, Mladen
AU  - Marković, Bojan
AU  - Kovačević, Milena
AU  - Rmandić, Milena
AU  - Tasić, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4296
AB  - The traditional concept of drug discovery is based on the occupancydriven pharmacology model. It implies the development of inhibitors occupying binding sites that directly affect protein functions. Therefore, proteins that do not have such binding sites are generally considered as pharmacologically intractable. Furthermore, drugs that act in this way must be administered in dosage regimens that often result in high systemic drug exposures in order to maintain sufficient protein inhibition. Thus, there is a risk of the onset of off-target binding and side effects. The landscape of drug discovery has been markedly changed since proteolysis targeting chimera (PROTAC) molecules emerged twenty years ago as a part of the event-driven pharmacology model. These are bifunctional molecules that harness the ubiquitin-proteasome system, and are composed of a ligand that binds the protein of interest (POI), a ligand that recruits E3 ubiquitin ligase (E3UL) and a linker that connects these two parts. Pharmacologically, PROTACs bring POI and E3UL into close proximity, which triggers the formation of a functional ternary complex POI-PROTAC-E3UL. This event drives polyubiquitination and subsequent POI degradation by the 26S proteasome. The development and exceptional properties of PROTAC molecules that brought them to clinical studies will be discussed in this paper. © 2022 Serbian Chemical Society. All rights reserved.
AB  - Традиционални концепт открића лекова базиран је на фармаколошком моделу заснованом на окупираности циљних протеина. То подразумева развој инхибитора који окупирају везујућа места директно повезана са функцијама протеина. Стога, протеини који немају таква везујућа места се генерално сматрају фармаколошки недодирљивим. Осим тога, лекови који делују на овакав начин морају се примењивати у режимима дозирања који често доводе до претеране системске изложености леку ради одржања довољне инхибиције протеина. Дакле, постоји ризик од појаве везивања лека ван свог примарног места дејства и нежељених ефеката. Окосница развоја лекова је значајно измењена откако су се појавили PROTAC (енг. proteolysis targeting chimera) молекули пре двадесет година као део фармаколошког модела заснованог на покретању догађаја који доводе до разградње циљних протеина. Ово су бифункционални молекули који користе убиквитин-протеазом систем, а састоје се од лиганда који се везује за протеин од инте- реса (POI), лиганда који регрутује Е3 убиквитин лигазу (E3UL) и линкера који повезује ова два дела. Фармаколошки, PROTAC молекули доводе POI и Е3UL у близину, што води формирању функционалног тернарног комплекса POI–PROTAC–Е3UL. Овај догађај води полиубиквитинацији и следственој деградацији POI 26S протеазомом. Развој и изу- зетна својства PROTAC молекула која су их довела до клиничких студија дискутовани су овом раду.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy
T1  - Деградација протеина индукована PROTAC молекулима као нова стратегија у развоју лекова
VL  - 87
IS  - 7-8
SP  - 785
EP  - 811
DO  - 10.2298/JSC211209027K
ER  - 

@article{
author = "Koravović, Mladen and Marković, Bojan and Kovačević, Milena and Rmandić, Milena and Tasić, Gordana",
year = "2022",
abstract = "The traditional concept of drug discovery is based on the occupancydriven pharmacology model. It implies the development of inhibitors occupying binding sites that directly affect protein functions. Therefore, proteins that do not have such binding sites are generally considered as pharmacologically intractable. Furthermore, drugs that act in this way must be administered in dosage regimens that often result in high systemic drug exposures in order to maintain sufficient protein inhibition. Thus, there is a risk of the onset of off-target binding and side effects. The landscape of drug discovery has been markedly changed since proteolysis targeting chimera (PROTAC) molecules emerged twenty years ago as a part of the event-driven pharmacology model. These are bifunctional molecules that harness the ubiquitin-proteasome system, and are composed of a ligand that binds the protein of interest (POI), a ligand that recruits E3 ubiquitin ligase (E3UL) and a linker that connects these two parts. Pharmacologically, PROTACs bring POI and E3UL into close proximity, which triggers the formation of a functional ternary complex POI-PROTAC-E3UL. This event drives polyubiquitination and subsequent POI degradation by the 26S proteasome. The development and exceptional properties of PROTAC molecules that brought them to clinical studies will be discussed in this paper. © 2022 Serbian Chemical Society. All rights reserved., Традиционални концепт открића лекова базиран је на фармаколошком моделу заснованом на окупираности циљних протеина. То подразумева развој инхибитора који окупирају везујућа места директно повезана са функцијама протеина. Стога, протеини који немају таква везујућа места се генерално сматрају фармаколошки недодирљивим. Осим тога, лекови који делују на овакав начин морају се примењивати у режимима дозирања који често доводе до претеране системске изложености леку ради одржања довољне инхибиције протеина. Дакле, постоји ризик од појаве везивања лека ван свог примарног места дејства и нежељених ефеката. Окосница развоја лекова је значајно измењена откако су се појавили PROTAC (енг. proteolysis targeting chimera) молекули пре двадесет година као део фармаколошког модела заснованог на покретању догађаја који доводе до разградње циљних протеина. Ово су бифункционални молекули који користе убиквитин-протеазом систем, а састоје се од лиганда који се везује за протеин од инте- реса (POI), лиганда који регрутује Е3 убиквитин лигазу (E3UL) и линкера који повезује ова два дела. Фармаколошки, PROTAC молекули доводе POI и Е3UL у близину, што води формирању функционалног тернарног комплекса POI–PROTAC–Е3UL. Овај догађај води полиубиквитинацији и следственој деградацији POI 26S протеазомом. Развој и изу- зетна својства PROTAC молекула која су их довела до клиничких студија дискутовани су овом раду.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy, Деградација протеина индукована PROTAC молекулима као нова стратегија у развоју лекова",
volume = "87",
number = "7-8",
pages = "785-811",
doi = "10.2298/JSC211209027K"
}

Koravović, M., Marković, B., Kovačević, M., Rmandić, M.,& Tasić, G.. (2022). Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 87(7-8), 785-811.
https://doi.org/10.2298/JSC211209027K

Koravović M, Marković B, Kovačević M, Rmandić M, Tasić G. Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy. in Journal of the Serbian Chemical Society. 2022;87(7-8):785-811.
doi:10.2298/JSC211209027K .

Koravović, Mladen, Marković, Bojan, Kovačević, Milena, Rmandić, Milena, Tasić, Gordana, "Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy" in Journal of the Serbian Chemical Society, 87, no. 7-8 (2022):785-811,
https://doi.org/10.2298/JSC211209027K . .

TY  - CONF
AU  - Čarapić, Marija
AU  - Marković, Bojan
AU  - Petković, Miloš
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4741
PB  - European Research Network on Signal Transduction CA18133
C3  - 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event
T1  - Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS
SP  - 74
EP  - 74
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4741
ER  - 

@conference{
author = "Čarapić, Marija and Marković, Bojan and Petković, Miloš and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
publisher = "European Research Network on Signal Transduction CA18133",
journal = "2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event",
title = "Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS",
pages = "74-74",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4741"
}

Čarapić, M., Marković, B., Petković, M., Nikolić, K.,& Agbaba, D.. (2022). Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS. in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event
European Research Network on Signal Transduction CA18133., 74-74.
https://hdl.handle.net/21.15107/rcub_farfar_4741

Čarapić M, Marković B, Petković M, Nikolić K, Agbaba D. Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS. in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event. 2022;:74-74.
https://hdl.handle.net/21.15107/rcub_farfar_4741 .

Čarapić, Marija, Marković, Bojan, Petković, Miloš, Nikolić, Katarina, Agbaba, Danica, "Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS" in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event (2022):74-74,
https://hdl.handle.net/21.15107/rcub_farfar_4741 .

TY  - CONF
AU  - Jeremić, Aleksandra
AU  - Vuković, Petar
AU  - Vezmar, Milica
AU  - Pešić, Danilo
AU  - Drakulić, Jelena
AU  - Milosavljević, Filip
AU  - Miljević, Čedo
AU  - Marković, Bojan
AU  - Marić-Bojović, Nađa
AU  - Jukić, Marin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4731
AB  - Background: Depression causes significant burden to the society world-wide. Escitalopram is a commonly prescribed antidepressant, predominantly metabolized by the polymorphic CYP2C19 enzyme; however, this drug isn’t always effective [1]. The CYP2C19 genotype determines the CYP2C19 enzymatic capacity and CYP2C19*2 is the main loss-of-function (Null) allele [2]. In the most psychiatric clinics worldwide, escitalopram therapy usually starts with the standard recommended dose of 10 mg/day, regardless of CYP2C19 genotype [3]. The objective of this study was the quantification of difference in the escitalopram exposure among patients between genetically associated CYP2C19 slow and normal metabolizers, considering also the body weight [4].

Methods: In this ongoing prospective cross sectional study, the drug concentration was measured in 53 outpatients treated with 10 mg of escitalopram, 2 weeks after treatment initiation, 24 hours after the last dose. Measured plasma concentration was 25-50 ng/ml was considered the ideal drug exposure. [5] If the drug concentration was 5-25 ng/ml, patients were classified as underdosed/underexposed, while patients with drug concentration <5ng/ml were classified as non-compliers and excluded from the further analysis. Patients were genotyped by polymerase chain reaction–based assay for the CYP2C19*2 allele. All participants were included from the Institute for Mental Health in Belgrade outpatient clinic and daily hospital. The patients were classified based on their CYP2C19 genotype; those carrying CYP2C19*2 variant alleles were categorized into slow metabolizer group, while non-carriers were categorized into normal metabolizer group. Difference in body weight and age between slow and metabolizer groups was analysed by the Mann-Whitney’s test. The effects of CYP2C19 metabolizer category (normal vs. slow metabolizer) and body weight on escitalopram plasma level were evaluated by the linear regression model.

Results: Out of 53 outpatients, who completed the study to date, 24 participants were slow metabolizers and 29 participants were normal metabolizers. After two weeks of treatment with 10mg of escitalopram, only 13 patients (24%) were within the therapeutic range (25-50ng/ml), no patient was underexposed, while the remaining 40 patients were underexposed. Median age body weight in the slow metabolizers group were 41 years [IQR: 27-47] and 77kg [IQR: 65-88,5], while in normal metabolizers group age and body weight were 35 years [IQR: 22-49] and 66kg [IQR: 59-88]. The drug level increase due to lower body weight and due to occurrence of CYP2C19*2 allele observed in the regression equation did not reach statistical significance.

Conclusion: While the result directionality was in accordance with the previously published studies, the effects of body weight and CYP2C19*2 allele occurrence were not significant in the analysed cohort. The absence of significant effects was likely due to still limited power of the study. Since this interim analysis includes only approximately one third of patients compared with what had been originally planned, it is expected that firmer conclusions related to the combined effect of CYP2C19 genotype and body weight on escitalopram exposure will emerge after all planned patients are included.
PB  - Elsevier
C3  - Neuroscience Applied
T1  - Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study
VL  - 1
IS  - Supplement 2
SP  - 330
EP  - 331
DO  - 10.1016/j.nsa.2022.100763
ER  - 

@conference{
author = "Jeremić, Aleksandra and Vuković, Petar and Vezmar, Milica and Pešić, Danilo and Drakulić, Jelena and Milosavljević, Filip and Miljević, Čedo and Marković, Bojan and Marić-Bojović, Nađa and Jukić, Marin",
year = "2022",
abstract = "Background: Depression causes significant burden to the society world-wide. Escitalopram is a commonly prescribed antidepressant, predominantly metabolized by the polymorphic CYP2C19 enzyme; however, this drug isn’t always effective [1]. The CYP2C19 genotype determines the CYP2C19 enzymatic capacity and CYP2C19*2 is the main loss-of-function (Null) allele [2]. In the most psychiatric clinics worldwide, escitalopram therapy usually starts with the standard recommended dose of 10 mg/day, regardless of CYP2C19 genotype [3]. The objective of this study was the quantification of difference in the escitalopram exposure among patients between genetically associated CYP2C19 slow and normal metabolizers, considering also the body weight [4].

Methods: In this ongoing prospective cross sectional study, the drug concentration was measured in 53 outpatients treated with 10 mg of escitalopram, 2 weeks after treatment initiation, 24 hours after the last dose. Measured plasma concentration was 25-50 ng/ml was considered the ideal drug exposure. [5] If the drug concentration was 5-25 ng/ml, patients were classified as underdosed/underexposed, while patients with drug concentration <5ng/ml were classified as non-compliers and excluded from the further analysis. Patients were genotyped by polymerase chain reaction–based assay for the CYP2C19*2 allele. All participants were included from the Institute for Mental Health in Belgrade outpatient clinic and daily hospital. The patients were classified based on their CYP2C19 genotype; those carrying CYP2C19*2 variant alleles were categorized into slow metabolizer group, while non-carriers were categorized into normal metabolizer group. Difference in body weight and age between slow and metabolizer groups was analysed by the Mann-Whitney’s test. The effects of CYP2C19 metabolizer category (normal vs. slow metabolizer) and body weight on escitalopram plasma level were evaluated by the linear regression model.

Results: Out of 53 outpatients, who completed the study to date, 24 participants were slow metabolizers and 29 participants were normal metabolizers. After two weeks of treatment with 10mg of escitalopram, only 13 patients (24%) were within the therapeutic range (25-50ng/ml), no patient was underexposed, while the remaining 40 patients were underexposed. Median age body weight in the slow metabolizers group were 41 years [IQR: 27-47] and 77kg [IQR: 65-88,5], while in normal metabolizers group age and body weight were 35 years [IQR: 22-49] and 66kg [IQR: 59-88]. The drug level increase due to lower body weight and due to occurrence of CYP2C19*2 allele observed in the regression equation did not reach statistical significance.

Conclusion: While the result directionality was in accordance with the previously published studies, the effects of body weight and CYP2C19*2 allele occurrence were not significant in the analysed cohort. The absence of significant effects was likely due to still limited power of the study. Since this interim analysis includes only approximately one third of patients compared with what had been originally planned, it is expected that firmer conclusions related to the combined effect of CYP2C19 genotype and body weight on escitalopram exposure will emerge after all planned patients are included.",
publisher = "Elsevier",
journal = "Neuroscience Applied",
title = "Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study",
volume = "1",
number = "Supplement 2",
pages = "330-331",
doi = "10.1016/j.nsa.2022.100763"
}

Jeremić, A., Vuković, P., Vezmar, M., Pešić, D., Drakulić, J., Milosavljević, F., Miljević, Č., Marković, B., Marić-Bojović, N.,& Jukić, M.. (2022). Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study. in Neuroscience Applied
Elsevier., 1(Supplement 2), 330-331.
https://doi.org/10.1016/j.nsa.2022.100763

Jeremić A, Vuković P, Vezmar M, Pešić D, Drakulić J, Milosavljević F, Miljević Č, Marković B, Marić-Bojović N, Jukić M. Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study. in Neuroscience Applied. 2022;1(Supplement 2):330-331.
doi:10.1016/j.nsa.2022.100763 .

Jeremić, Aleksandra, Vuković, Petar, Vezmar, Milica, Pešić, Danilo, Drakulić, Jelena, Milosavljević, Filip, Miljević, Čedo, Marković, Bojan, Marić-Bojović, Nađa, Jukić, Marin, "Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study" in Neuroscience Applied, 1, no. Supplement 2 (2022):330-331,
https://doi.org/10.1016/j.nsa.2022.100763 . .

TY  - CONF
AU  - Čarapić, Marija
AU  - Marković, Bojan
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4600
AB  - Ziprasidone, bensiothiasol piperazynylindolone derivative is second generation
antipsychotic drug used for the treatment of schizophrenia and in acute maniac/mixed
episodes associated with bipolar disorder. It has unique G-protein coupled receptor binding
profile with relatively low propensity for weight gain (1). Recently, it became an official
active pharmaceutical ingredient in European Pharmacopoeia, where there are three official
chromatographic systems, one for the assay and two other for early-eluiting and late-eluting
impurities. Therefore, the purpose of this investigation was to develop and validate a fast,
highly sensitive UHPLC-MS/MS method for the analysis of ziprasidone and its five impurities,
significantly differing in polarity and pKa. Separation was performed using Thermo ACCELA
UHPLC system (Thermo Scientific, Waltham, MA, USA) equipped with triple quad Mass
Spectrometer Thermo TSQ Quantum Access Max (Thermo Scientific, Waltham, MA, USA)
with a heated electro-spray ionization interface. Satisfactory chromatographic separation
was achieved using a gradient elution with mobile phase A (10mM ammonium formate
buffer, pH 4.7) and mobile phase B (acetonitrile) on a Acquity UPLC BEH C18 (50×2.1 mm,
1.7 μm) column with mobile phase flow rate of 300 μL/min. Sample injection volume was 10
μL. The analysis runtime was 7 minutes. The method was validated according to the
International Conference of Harmonization (ICH) guidelines and validation included
parameters such as specificity, linearity, accuracy, precision, limit of quantification and limit
of detection. The proposed rapid and sensitive method is convenient and reliable for the
assay and purity control in raw materials and in dosage forms (2).
AB  - Ziprasidon, derivat benzizotiazol piperazinilindolona, je antipsihotik druge generacije
koji se koristi za lečenje šizofrenije, kod akutnih maničnih ili mešovitih epizoda povezanih sa
bipolarnim poremećajem. Ima jedinstveni profil vezivanja za G protein-spregnute receptore
(GPCR) i relativno retko neželjeno dejstvo povećanja telesne težine (1). Nedavno je
monografija dve soli ziprasidona postala oficinalna u Evropskoj farmakopeji u kojoj se
ispitivanje vrši pomoću tri hromatografska sistema: ispitivanje sadržaja i dva odvojena
sistema za više i manje polarne nečistoće. Svrha ovog istraživanja bila da se razvije i validira
brza i visoko osetljiva UHPLC-MS/MS metoda za istovremeno ispitivanje ziprasidona i
njegovih pet nečistoća, koje se značajno razlikuju po polarnosti i pKa. Hromatografska
analiza je vršena na Thermo ACCELA UHPLC sistemu koji je spregnut sa tripl kvadrupolskim
masenim analizatorom Thermo TSQ Quantum Access Max (Thermo Scientific, Valtham, MA,
USA) sa elektrosprej jonizacijom na povišenoj temperaturi (HESI) kao jonskim izvorom.
Zadovoljavajuće razdvajanje dobijeno je korišć enjem gradijentog eluiranja sa mobilnom
fazom A (10 mM amonijum-formijat, pH 4,7) i mobilnom fazom B (acetonitril) na Acquity
UPLC BEH 50×2,1 mm, 1,7 μm (Waters) stacionarnoj fazi na temperaturi od 30ºC i pri
protoku mobilne faze od 300 μL/min. Zapremina injektovanja ispitivanih rastvora bila je
10 μL. Trajanje analize je 7 minuta (2). Metoda je validirana u skladu sa ICH (International
Council for Harmonisation) smernicom i pokazana je specifičnost metode, linearnost,
tačnost, preciznost, limit kvantifikacije i limit detekcije. Potvrđeno je da se brza i osetljiva
UHPLC-MS/MS metoda može primeniti za ispitivanje ziprasidona i njegovih nečistoća u
aktivnoj supstanci i doziranim oblicima.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities
T1  - Razvoj i validacija UHPLC‐MS/MS metode za ispitivanje ziprasidona i njegovih nečistoća
VL  - 72
IS  - 4 suplement
SP  - S536
EP  - S537
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4600
ER  - 

@conference{
author = "Čarapić, Marija and Marković, Bojan and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
abstract = "Ziprasidone, bensiothiasol piperazynylindolone derivative is second generation
antipsychotic drug used for the treatment of schizophrenia and in acute maniac/mixed
episodes associated with bipolar disorder. It has unique G-protein coupled receptor binding
profile with relatively low propensity for weight gain (1). Recently, it became an official
active pharmaceutical ingredient in European Pharmacopoeia, where there are three official
chromatographic systems, one for the assay and two other for early-eluiting and late-eluting
impurities. Therefore, the purpose of this investigation was to develop and validate a fast,
highly sensitive UHPLC-MS/MS method for the analysis of ziprasidone and its five impurities,
significantly differing in polarity and pKa. Separation was performed using Thermo ACCELA
UHPLC system (Thermo Scientific, Waltham, MA, USA) equipped with triple quad Mass
Spectrometer Thermo TSQ Quantum Access Max (Thermo Scientific, Waltham, MA, USA)
with a heated electro-spray ionization interface. Satisfactory chromatographic separation
was achieved using a gradient elution with mobile phase A (10mM ammonium formate
buffer, pH 4.7) and mobile phase B (acetonitrile) on a Acquity UPLC BEH C18 (50×2.1 mm,
1.7 μm) column with mobile phase flow rate of 300 μL/min. Sample injection volume was 10
μL. The analysis runtime was 7 minutes. The method was validated according to the
International Conference of Harmonization (ICH) guidelines and validation included
parameters such as specificity, linearity, accuracy, precision, limit of quantification and limit
of detection. The proposed rapid and sensitive method is convenient and reliable for the
assay and purity control in raw materials and in dosage forms (2)., Ziprasidon, derivat benzizotiazol piperazinilindolona, je antipsihotik druge generacije
koji se koristi za lečenje šizofrenije, kod akutnih maničnih ili mešovitih epizoda povezanih sa
bipolarnim poremećajem. Ima jedinstveni profil vezivanja za G protein-spregnute receptore
(GPCR) i relativno retko neželjeno dejstvo povećanja telesne težine (1). Nedavno je
monografija dve soli ziprasidona postala oficinalna u Evropskoj farmakopeji u kojoj se
ispitivanje vrši pomoću tri hromatografska sistema: ispitivanje sadržaja i dva odvojena
sistema za više i manje polarne nečistoće. Svrha ovog istraživanja bila da se razvije i validira
brza i visoko osetljiva UHPLC-MS/MS metoda za istovremeno ispitivanje ziprasidona i
njegovih pet nečistoća, koje se značajno razlikuju po polarnosti i pKa. Hromatografska
analiza je vršena na Thermo ACCELA UHPLC sistemu koji je spregnut sa tripl kvadrupolskim
masenim analizatorom Thermo TSQ Quantum Access Max (Thermo Scientific, Valtham, MA,
USA) sa elektrosprej jonizacijom na povišenoj temperaturi (HESI) kao jonskim izvorom.
Zadovoljavajuće razdvajanje dobijeno je korišć enjem gradijentog eluiranja sa mobilnom
fazom A (10 mM amonijum-formijat, pH 4,7) i mobilnom fazom B (acetonitril) na Acquity
UPLC BEH 50×2,1 mm, 1,7 μm (Waters) stacionarnoj fazi na temperaturi od 30ºC i pri
protoku mobilne faze od 300 μL/min. Zapremina injektovanja ispitivanih rastvora bila je
10 μL. Trajanje analize je 7 minuta (2). Metoda je validirana u skladu sa ICH (International
Council for Harmonisation) smernicom i pokazana je specifičnost metode, linearnost,
tačnost, preciznost, limit kvantifikacije i limit detekcije. Potvrđeno je da se brza i osetljiva
UHPLC-MS/MS metoda može primeniti za ispitivanje ziprasidona i njegovih nečistoća u
aktivnoj supstanci i doziranim oblicima.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities, Razvoj i validacija UHPLC‐MS/MS metode za ispitivanje ziprasidona i njegovih nečistoća",
volume = "72",
number = "4 suplement",
pages = "S536-S537",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4600"
}

Čarapić, M., Marković, B., Nikolić, K.,& Agbaba, D.. (2022). Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S536-S537.
https://hdl.handle.net/21.15107/rcub_farfar_4600

Čarapić M, Marković B, Nikolić K, Agbaba D. Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities. in Arhiv za farmaciju. 2022;72(4 suplement):S536-S537.
https://hdl.handle.net/21.15107/rcub_farfar_4600 .

Čarapić, Marija, Marković, Bojan, Nikolić, Katarina, Agbaba, Danica, "Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S536-S537,
https://hdl.handle.net/21.15107/rcub_farfar_4600 .

TY  - CONF
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, Jovana
AU  - Marković, Bojan
AU  - Vujić, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4605
AB  - The serotonin receptor ligands, such as structurally related arylpiperazine and
benzothiazepine derivatives, are most commonly used in the treatment of schizophrenia,
depression, and manic disorders. (1). Due to emphasized lipophilicity, their retention can be
successfully defined under the reversed-phase (RP) chromatographic conditions. Using the
experimental design methodology (2), the retention of selected serotonin receptor ligands
(aripiprazole, ziprasidone, risperidone, olanzapine, quetiapine, mirtazapine) was tested on
RP stationary phases, in order to define differences in their retention mechanisms and
ensure the further optimization of separation conditions. The silica modified, C8 and
pentafluorophenylpropyl (PFP) columns were used as stationary phases, while the mobile
phase was a mixture of acetonitrile and ammonium acetate. The experimental plan was
defined according to the central composite design varying the following factors: ammonium
acetate concentration (15-25 mM), volume fraction of acetonitrile (40-50% v/v), and column
temperature (20-30°C). The differences between retention on C8 and PFP columns were
presented by using the radar plots and principal component analysis. The obtained
differences are especially visible in the case of ziprasidone, olanzapine, quetiapine and
mirtazapine, which may explain the occurrence of inversions in their elution order. On C8
phase the separation of structurally related arylpiperazine or benzothiazepine derivatives
was achieved, while the PFP phase showed more successful applicability in the separation of
all tested ligands. The slightly higher values of the selectivity parameter were obtained for
40% of acetonitrile in the mobile phase. In further optimization of the separation conditions,
the PFP bonded stationary phase can be successfully applied.
AB  - Ligandi serotoninskih receptora kao što su strukturno srodni derivati arilpiperazina i
benzotiazepina, najčešće se koriste u terapiji oboljenja centralnog nervnog sistema, poput
šizofrenije, depresije, ili maničnog poremećaja (1). Zbog izraženih lipofilnih karakteristika,
njihovo retenciono ponašanje se može uspešno definisati u uslovima reverzno-fazne
(Reversed‐Phase, RP) tečne hromatografije. Primenom metodologije eksperimentalnog
dizajna (2), retencione karakteristike odabranih liganada serotoninskih receptora
(aripiprazol, ziprazidon, risperidon, olanzapin, kvetiapin, mirtazapin) su ispitane na RP
stacionarnim fazama, sa ciljem definisanja razlika u mehanizmima zadržavanja i daljoj
optimizaciji hromatografskih uslova razdvajanja. Kao stacionarne faze korišćene su C8 i
pentafluorofenilpropil (PFP) kolone, dok je mobilna faza bila smeša acetonitrila i amonijum-
acetata. Plan izvođenja eksperimenta je postavljen prema planu centralnog kompozitnog
dizajna variranjem sledećih hromatografskih faktora: koncentracije amonijum-acetata (15-
25 mM), zapreminskog udela acetonitrila (40-50% v/v) i temperature kolone (20-30°C).
Primenom linearne regresione analize, definisan je uticaj izabranih faktora na promenu
retencionog ponašanja (k) ispitivanih liganada. Korišćenjem radar grafika i primenom
analize glavnih komponenti predstavljene su razlike između mehanizama zadržavanja na C8
i PFP kolonama. Razlike su posebno vidljive u slučaju ziprazidona, olanzapina, kvetiapina i
mirtazapina čime se može objasniti inverzija u njihovom redosledu eluiranja. Uočeno je da
C8 stacionarna faza pogoduje razdvajanju strukturno srodnih arilpiperazina ili strukturno
srodnih derivata benzotiazepina, dok je PFP stacionarna faza pokazala uspešniju
primenljivost u razdvajanju svih ispitivanih liganada. Nešto veće vrednosti parametra
selektivnosti dobijene su na 40% udelu acetonitrila u mobilnoj fazi. U daljoj optimizaciji
hromatografskih uslova razdvajanja ispitivanih liganada, stacionarna faza sa vezanim PFP
grupama se može uspešno primeniti.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography
T1  - Ptimizacija reverzno‐faznih uslova za razdvajanje liganada serotoninskih receptora u tečnoj hromatografiji
VL  - 72
IS  - 4 suplement
SP  - S548
EP  - S549
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4605
ER  - 

@conference{
author = "Obradović, Darija and Savić, Jelena and Joksimović, Jovana and Marković, Bojan and Vujić, Zorica",
year = "2022",
abstract = "The serotonin receptor ligands, such as structurally related arylpiperazine and
benzothiazepine derivatives, are most commonly used in the treatment of schizophrenia,
depression, and manic disorders. (1). Due to emphasized lipophilicity, their retention can be
successfully defined under the reversed-phase (RP) chromatographic conditions. Using the
experimental design methodology (2), the retention of selected serotonin receptor ligands
(aripiprazole, ziprasidone, risperidone, olanzapine, quetiapine, mirtazapine) was tested on
RP stationary phases, in order to define differences in their retention mechanisms and
ensure the further optimization of separation conditions. The silica modified, C8 and
pentafluorophenylpropyl (PFP) columns were used as stationary phases, while the mobile
phase was a mixture of acetonitrile and ammonium acetate. The experimental plan was
defined according to the central composite design varying the following factors: ammonium
acetate concentration (15-25 mM), volume fraction of acetonitrile (40-50% v/v), and column
temperature (20-30°C). The differences between retention on C8 and PFP columns were
presented by using the radar plots and principal component analysis. The obtained
differences are especially visible in the case of ziprasidone, olanzapine, quetiapine and
mirtazapine, which may explain the occurrence of inversions in their elution order. On C8
phase the separation of structurally related arylpiperazine or benzothiazepine derivatives
was achieved, while the PFP phase showed more successful applicability in the separation of
all tested ligands. The slightly higher values of the selectivity parameter were obtained for
40% of acetonitrile in the mobile phase. In further optimization of the separation conditions,
the PFP bonded stationary phase can be successfully applied., Ligandi serotoninskih receptora kao što su strukturno srodni derivati arilpiperazina i
benzotiazepina, najčešće se koriste u terapiji oboljenja centralnog nervnog sistema, poput
šizofrenije, depresije, ili maničnog poremećaja (1). Zbog izraženih lipofilnih karakteristika,
njihovo retenciono ponašanje se može uspešno definisati u uslovima reverzno-fazne
(Reversed‐Phase, RP) tečne hromatografije. Primenom metodologije eksperimentalnog
dizajna (2), retencione karakteristike odabranih liganada serotoninskih receptora
(aripiprazol, ziprazidon, risperidon, olanzapin, kvetiapin, mirtazapin) su ispitane na RP
stacionarnim fazama, sa ciljem definisanja razlika u mehanizmima zadržavanja i daljoj
optimizaciji hromatografskih uslova razdvajanja. Kao stacionarne faze korišćene su C8 i
pentafluorofenilpropil (PFP) kolone, dok je mobilna faza bila smeša acetonitrila i amonijum-
acetata. Plan izvođenja eksperimenta je postavljen prema planu centralnog kompozitnog
dizajna variranjem sledećih hromatografskih faktora: koncentracije amonijum-acetata (15-
25 mM), zapreminskog udela acetonitrila (40-50% v/v) i temperature kolone (20-30°C).
Primenom linearne regresione analize, definisan je uticaj izabranih faktora na promenu
retencionog ponašanja (k) ispitivanih liganada. Korišćenjem radar grafika i primenom
analize glavnih komponenti predstavljene su razlike između mehanizama zadržavanja na C8
i PFP kolonama. Razlike su posebno vidljive u slučaju ziprazidona, olanzapina, kvetiapina i
mirtazapina čime se može objasniti inverzija u njihovom redosledu eluiranja. Uočeno je da
C8 stacionarna faza pogoduje razdvajanju strukturno srodnih arilpiperazina ili strukturno
srodnih derivata benzotiazepina, dok je PFP stacionarna faza pokazala uspešniju
primenljivost u razdvajanju svih ispitivanih liganada. Nešto veće vrednosti parametra
selektivnosti dobijene su na 40% udelu acetonitrila u mobilnoj fazi. U daljoj optimizaciji
hromatografskih uslova razdvajanja ispitivanih liganada, stacionarna faza sa vezanim PFP
grupama se može uspešno primeniti.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography, Ptimizacija reverzno‐faznih uslova za razdvajanje liganada serotoninskih receptora u tečnoj hromatografiji",
volume = "72",
number = "4 suplement",
pages = "S548-S549",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4605"
}

Obradović, D., Savić, J., Joksimović, J., Marković, B.,& Vujić, Z.. (2022). Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S548-S549.
https://hdl.handle.net/21.15107/rcub_farfar_4605

Obradović D, Savić J, Joksimović J, Marković B, Vujić Z. Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography. in Arhiv za farmaciju. 2022;72(4 suplement):S548-S549.
https://hdl.handle.net/21.15107/rcub_farfar_4605 .

Obradović, Darija, Savić, Jelena, Joksimović, Jovana, Marković, Bojan, Vujić, Zorica, "Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S548-S549,
https://hdl.handle.net/21.15107/rcub_farfar_4605 .

TY  - JOUR
AU  - Đoković, Jelena
AU  - Savić, Sanela
AU  - Mitrović, Jelena
AU  - Nikolić, Ines
AU  - Marković, Bojan
AU  - Ranđelović, Danijela
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Cekić, Nebojša
AU  - Stevanović, Vladimir
AU  - Batinić, Bojan
AU  - Aranđelović, Jovana
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5541
AB  - The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats
VL  - 22
IS  - 15
DO  - 10.3390/ijms22157991
ER  - 

@article{
author = "Đoković, Jelena and Savić, Sanela and Mitrović, Jelena and Nikolić, Ines and Marković, Bojan and Ranđelović, Danijela and Antić-Stanković, Jelena and Božić, Dragana and Cekić, Nebojša and Stevanović, Vladimir and Batinić, Bojan and Aranđelović, Jovana and Savić, Miroslav and Savić, Snežana",
year = "2021",
abstract = "The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats",
volume = "22",
number = "15",
doi = "10.3390/ijms22157991"
}

Đoković, J., Savić, S., Mitrović, J., Nikolić, I., Marković, B., Ranđelović, D., Antić-Stanković, J., Božić, D., Cekić, N., Stevanović, V., Batinić, B., Aranđelović, J., Savić, M.,& Savić, S.. (2021). Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats. in International Journal of Molecular Sciences
MDPI., 22(15).
https://doi.org/10.3390/ijms22157991

Đoković J, Savić S, Mitrović J, Nikolić I, Marković B, Ranđelović D, Antić-Stanković J, Božić D, Cekić N, Stevanović V, Batinić B, Aranđelović J, Savić M, Savić S. Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats. in International Journal of Molecular Sciences. 2021;22(15).
doi:10.3390/ijms22157991 .

Đoković, Jelena, Savić, Sanela, Mitrović, Jelena, Nikolić, Ines, Marković, Bojan, Ranđelović, Danijela, Antić-Stanković, Jelena, Božić, Dragana, Cekić, Nebojša, Stevanović, Vladimir, Batinić, Bojan, Aranđelović, Jovana, Savić, Miroslav, Savić, Snežana, "Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats" in International Journal of Molecular Sciences, 22, no. 15 (2021),
https://doi.org/10.3390/ijms22157991 . .

TY  - JOUR
AU  - Jeremić, Aleksandra
AU  - Milosavljević, Filip
AU  - Vladimirov, Sandra
AU  - Batinić, Bojan
AU  - Marković, Bojan
AU  - Jukić, Marin
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4733
AB  - Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic
drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the
method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was
deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the
mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded
in the MRM mode by using a positive electrospray source with tandem mass spectrometry
detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram
(8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant
concentrations for each drug. Coefficients of determination (R2
) were higher than 0.99, while the
relative difference between nominal and measured concentrations (RE) and CV were lower than
15% for all targets. High performance liquid chromatography coupled with the mass detector
(HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone
366
and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy,
precision, matrix effect and stability. This method has significant advantages in terms of low
sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4
minutes).
AB  - Simultana kvantifikacija većeg broja psihijatrijskih lekova je 
važna za terapijsko praćenje 
psihijatrijskih  pacijenata.  Takođe
,  od  značaja  iz  praktičnih  ra
zloga  bi  bilo  da  metoda  bude 
jednostavna,  laka  za  izvođenje  i 
da  ne  zahteva  puno  vremena.  Uz
orak  plazme  (200  μl)  je 
deproteinizovan i izvršeno je h
romatografsko razdvajanje lekova
 na 
ZORBAX Eclipse XDB-
Phenyl  koloni  sa  mobilnom  fazom  sačinjenom  od  acetonitrila  i  vo
denog  rastvora 
0,1% 
mravlje kiseline
 (
60:40, v/v). Maseni spektri snimani su u MRM modu korišćenjem i
zvora sa 
elektrosprej pozitivnom jonizacijom i tandemske masene detekcij
e. Ispitivani opseg koncentracija 
bio je 2–256 ng/ml za sve analizirane lekove, osim za escitalop
ram, gde je bio 8-256 ng/ml. 
Kontrolni  uzorci  su  pripremani  u
  kvintuplikatu  u  tri  relevantne
  koncentracije  za  svaki  lek. 
Determinacioni koeficijenti (R
2
) bili su veći od 0,99, dok su relativna razlika između nominal
nih 
i merenih koncentracija (RV) i koeficijent varijacije (CV) bili
 manji od 15% za sve analite. 
Metoda  tečne  hromatografije  visoki
h  performansi  uparena  sa  tand
em  masenim  detektorom 
(HPLC-MS/MS) je validirana u pogledu selektivnosti, linearnosti
, tačnosti, preciznosti, efekata 
matriksa  i  stabilnosti  za  simultano  određivanje 
sertralina,  escitaloprama,  risperidona  i 
paliperidona u humanoj plazmi. Metoda zahteva malu zapreminu uz
orka (200 μl), kratke pripreme 
uzorka (3 sata) i kratko vreme tr
ajanja pojedinačnog merenja (4
 minuta).
T2  - Arhiv za farmaciju
T1  - Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma
T1  - Validacija brze i jednostavne hromatografske 
metode za simultanu kvantifikaciju nivoa 
sertralina, escitaloprama, risperidona i 
paliperidona u humanoj plazmi
VL  - 71
IS  - 5
SP  - 365
EP  - 377
DO  - 10.5937/arhfarm71-31163
ER  - 

@article{
author = "Jeremić, Aleksandra and Milosavljević, Filip and Vladimirov, Sandra and Batinić, Bojan and Marković, Bojan and Jukić, Marin",
year = "2021",
abstract = "Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic
drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the
method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was
deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the
mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded
in the MRM mode by using a positive electrospray source with tandem mass spectrometry
detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram
(8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant
concentrations for each drug. Coefficients of determination (R2
) were higher than 0.99, while the
relative difference between nominal and measured concentrations (RE) and CV were lower than
15% for all targets. High performance liquid chromatography coupled with the mass detector
(HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone
366
and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy,
precision, matrix effect and stability. This method has significant advantages in terms of low
sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4
minutes)., Simultana kvantifikacija većeg broja psihijatrijskih lekova je 
važna za terapijsko praćenje 
psihijatrijskih  pacijenata.  Takođe
,  od  značaja  iz  praktičnih  ra
zloga  bi  bilo  da  metoda  bude 
jednostavna,  laka  za  izvođenje  i 
da  ne  zahteva  puno  vremena.  Uz
orak  plazme  (200  μl)  je 
deproteinizovan i izvršeno je h
romatografsko razdvajanje lekova
 na 
ZORBAX Eclipse XDB-
Phenyl  koloni  sa  mobilnom  fazom  sačinjenom  od  acetonitrila  i  vo
denog  rastvora 
0,1% 
mravlje kiseline
 (
60:40, v/v). Maseni spektri snimani su u MRM modu korišćenjem i
zvora sa 
elektrosprej pozitivnom jonizacijom i tandemske masene detekcij
e. Ispitivani opseg koncentracija 
bio je 2–256 ng/ml za sve analizirane lekove, osim za escitalop
ram, gde je bio 8-256 ng/ml. 
Kontrolni  uzorci  su  pripremani  u
  kvintuplikatu  u  tri  relevantne
  koncentracije  za  svaki  lek. 
Determinacioni koeficijenti (R
2
) bili su veći od 0,99, dok su relativna razlika između nominal
nih 
i merenih koncentracija (RV) i koeficijent varijacije (CV) bili
 manji od 15% za sve analite. 
Metoda  tečne  hromatografije  visoki
h  performansi  uparena  sa  tand
em  masenim  detektorom 
(HPLC-MS/MS) je validirana u pogledu selektivnosti, linearnosti
, tačnosti, preciznosti, efekata 
matriksa  i  stabilnosti  za  simultano  određivanje 
sertralina,  escitaloprama,  risperidona  i 
paliperidona u humanoj plazmi. Metoda zahteva malu zapreminu uz
orka (200 μl), kratke pripreme 
uzorka (3 sata) i kratko vreme tr
ajanja pojedinačnog merenja (4
 minuta).",
journal = "Arhiv za farmaciju",
title = "Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma, Validacija brze i jednostavne hromatografske 
metode za simultanu kvantifikaciju nivoa 
sertralina, escitaloprama, risperidona i 
paliperidona u humanoj plazmi",
volume = "71",
number = "5",
pages = "365-377",
doi = "10.5937/arhfarm71-31163"
}

Jeremić, A., Milosavljević, F., Vladimirov, S., Batinić, B., Marković, B.,& Jukić, M.. (2021). Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma. in Arhiv za farmaciju, 71(5), 365-377.
https://doi.org/10.5937/arhfarm71-31163

Jeremić A, Milosavljević F, Vladimirov S, Batinić B, Marković B, Jukić M. Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma. in Arhiv za farmaciju. 2021;71(5):365-377.
doi:10.5937/arhfarm71-31163 .

Jeremić, Aleksandra, Milosavljević, Filip, Vladimirov, Sandra, Batinić, Bojan, Marković, Bojan, Jukić, Marin, "Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma" in Arhiv za farmaciju, 71, no. 5 (2021):365-377,
https://doi.org/10.5937/arhfarm71-31163 . .

TY  - JOUR
AU  - Koravović, Mladen
AU  - Tasić, Gordana
AU  - Rmandić, Milena
AU  - Marković, Bojan
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3918
AB  - Traditional drug discovery strategies are usually focused on occupancy of binding sites that directly affect functions of proteins. Hence, proteins that lack such binding sites are generally considered pharmacologically intractable. Modulators of protein activity, especially inhibitors, must be applied in appropriate dosage regimens that often lead to high systemic drug exposures in  order  to  maintain  sufficient  protein  inhibition in  vivo.  Consequently,  there  is  a  risk  of undesirable off-target drug binding and side effects. Recently, PROteolysis TArgeting Chimera (PROTAC) technology has emerged as a new pharmacological modality that exploits PROTAC molecules for induced protein degradation. PROTAC molecule is a heterobifunctional structure consisting of a ligand that binds a protein of interest (POI), a ligand for recruiting an E3 ubiquitin ligase (an enzyme involved in the POI ubiquitination) and a linker that connects these two. After POI-PROTAC-E3 ubiquitin ligase ternary complex formation, the POI undergoes ubiquitination (an enzymatic post-translational modification in which ubiquitin is attached to the POI) and degradation.  By  merging  the  principles  of  photopharmacology  and  PROTAC  technology, photocontrollable PROTACs for spatiotemporal control of induced protein degradation have recently emerged. The main advantage of photocontrollable over conventional PROTACs is the possible prevention of off-target toxicity thanks to local photoactivation.
AB  - Tradicionalne strategije razvoja lekova su obično osvrnute na okupiranje vezujućih mesta koja direktno utiču na funkcije proteina. Stoga se proteini koji nemaju takva vezujuća mesta generalno smatraju farmakološki nedodirljivim. Modulatori aktivnosti proteina, naročito inhibitori, koriste se u režimima doziranja koji često dovode do preterane sistemske izloženosti leku, a sve u cilju održavanja dovoljne inhibicije proteina in vivo. Posledično, postoji rizik od neželjenog vezivanja leka van svog primarnog mesta dejstva i neželjenih efekata. Nedavno je predstavljena tehnologija dirigovane proteolize (PROteolysis TArgeting Chimera, PROTAC) kao novi farmakološki modalitet koji koristi PROTAC molekule za indukovanu degradaciju proteina. PROTAC molekuli su heterobifunkcionalne strukture sačinjene od liganda koji se vezuje za protein od interesa (POI), liganda za regrutovanje E3 ubikvitin ligaze (enzima uključenog u ubikvitinaciju POI) i linkera koji ih povezuje. Nakon formiranja ternarnog kompleksa POI-PROTAC-E3 ubikvitin ligaza, POI podleže ubikvitinaciji (enzimskoj post-translacionoj modifikaciji u kojoj se ubikvitin vezuje za POI) i degradaciji. Integrisanjem principa fotofarmakologije i PROTAC tehnologije, nedavno su nastali su fotokontrolisani PROTAC molekuli za prostorno-vremensku kontrolu indukovane degradacije proteina. Zahvaljujući lokalnoj fotoaktivaciji, glavna prednost fotokontrolisanih nad konvencionalnim PROTAC molekulima je moguća prevencija toksičnosti koja nastaje usled dejstva van primarnog biološkog targeta.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Photocontrollable PROTAC molecules – structure and mechanism of action
T1  - Fotokontrolisani PROTAC molekuli - struktura i mehanizam dejstva
VL  - 71
IS  - 3
SP  - 161
EP  - 176
DO  - 10.5937/arhfarm71‐30785
ER  - 

@article{
author = "Koravović, Mladen and Tasić, Gordana and Rmandić, Milena and Marković, Bojan",
year = "2021",
abstract = "Traditional drug discovery strategies are usually focused on occupancy of binding sites that directly affect functions of proteins. Hence, proteins that lack such binding sites are generally considered pharmacologically intractable. Modulators of protein activity, especially inhibitors, must be applied in appropriate dosage regimens that often lead to high systemic drug exposures in  order  to  maintain  sufficient  protein  inhibition in  vivo.  Consequently,  there  is  a  risk  of undesirable off-target drug binding and side effects. Recently, PROteolysis TArgeting Chimera (PROTAC) technology has emerged as a new pharmacological modality that exploits PROTAC molecules for induced protein degradation. PROTAC molecule is a heterobifunctional structure consisting of a ligand that binds a protein of interest (POI), a ligand for recruiting an E3 ubiquitin ligase (an enzyme involved in the POI ubiquitination) and a linker that connects these two. After POI-PROTAC-E3 ubiquitin ligase ternary complex formation, the POI undergoes ubiquitination (an enzymatic post-translational modification in which ubiquitin is attached to the POI) and degradation.  By  merging  the  principles  of  photopharmacology  and  PROTAC  technology, photocontrollable PROTACs for spatiotemporal control of induced protein degradation have recently emerged. The main advantage of photocontrollable over conventional PROTACs is the possible prevention of off-target toxicity thanks to local photoactivation., Tradicionalne strategije razvoja lekova su obično osvrnute na okupiranje vezujućih mesta koja direktno utiču na funkcije proteina. Stoga se proteini koji nemaju takva vezujuća mesta generalno smatraju farmakološki nedodirljivim. Modulatori aktivnosti proteina, naročito inhibitori, koriste se u režimima doziranja koji često dovode do preterane sistemske izloženosti leku, a sve u cilju održavanja dovoljne inhibicije proteina in vivo. Posledično, postoji rizik od neželjenog vezivanja leka van svog primarnog mesta dejstva i neželjenih efekata. Nedavno je predstavljena tehnologija dirigovane proteolize (PROteolysis TArgeting Chimera, PROTAC) kao novi farmakološki modalitet koji koristi PROTAC molekule za indukovanu degradaciju proteina. PROTAC molekuli su heterobifunkcionalne strukture sačinjene od liganda koji se vezuje za protein od interesa (POI), liganda za regrutovanje E3 ubikvitin ligaze (enzima uključenog u ubikvitinaciju POI) i linkera koji ih povezuje. Nakon formiranja ternarnog kompleksa POI-PROTAC-E3 ubikvitin ligaza, POI podleže ubikvitinaciji (enzimskoj post-translacionoj modifikaciji u kojoj se ubikvitin vezuje za POI) i degradaciji. Integrisanjem principa fotofarmakologije i PROTAC tehnologije, nedavno su nastali su fotokontrolisani PROTAC molekuli za prostorno-vremensku kontrolu indukovane degradacije proteina. Zahvaljujući lokalnoj fotoaktivaciji, glavna prednost fotokontrolisanih nad konvencionalnim PROTAC molekulima je moguća prevencija toksičnosti koja nastaje usled dejstva van primarnog biološkog targeta.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Photocontrollable PROTAC molecules – structure and mechanism of action, Fotokontrolisani PROTAC molekuli - struktura i mehanizam dejstva",
volume = "71",
number = "3",
pages = "161-176",
doi = "10.5937/arhfarm71‐30785"
}

Koravović, M., Tasić, G., Rmandić, M.,& Marković, B.. (2021). Photocontrollable PROTAC molecules – structure and mechanism of action. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(3), 161-176.
https://doi.org/10.5937/arhfarm71‐30785

Koravović M, Tasić G, Rmandić M, Marković B. Photocontrollable PROTAC molecules – structure and mechanism of action. in Arhiv za farmaciju. 2021;71(3):161-176.
doi:10.5937/arhfarm71‐30785 .

Koravović, Mladen, Tasić, Gordana, Rmandić, Milena, Marković, Bojan, "Photocontrollable PROTAC molecules – structure and mechanism of action" in Arhiv za farmaciju, 71, no. 3 (2021):161-176,
https://doi.org/10.5937/arhfarm71‐30785 . .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Marodi, Marko
AU  - Marković, Bojan
AU  - Tomašič, Tihomir
AU  - Zidar, Nace
AU  - Peterlin Mašič, Lucija
AU  - Ilaš, Janez
AU  - Kikelj, Danijel
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5460
AB  - In this study, estimation of gastrointestinal absorption of thirteen selected dual DNA gyrase and topoisomerase IV
inhibitors was carried out using PAMPA test. Diffusion through artificial membrane, consisting of egg lecithin solution
in dodecane (first PAMPA model) and a mixture of hexadecane and hexane (second PAMPA model), was monitored
[1,2]. The starting solutions (pH 5.5) and the acceptor medium (pH 7.4) were prepared to contain 2% dimethyl
sulfoxide. Concentrations of tested compounds in starting solutions, donor and acceptor medium after incubation
were measured using LC-MS/MS method. Permeability coefficients were calculated and good correlation was
observed between results obtained using these two PAMPA models. Subsequently, the hexadecane/hexane model
was selected for the evaluation of gastrointestinal absorption of the remaining ten compounds.
Derivatives with the highest permeability in hexadecane/hexane model were TZS-34 and TCF-3a (logPe: -5.37 and
-4.93, respectively) whereas TLK-13 and NZ-97 had the lowest permeability (logPe: -9.91 and -9.85, respectively).
Therefore, the highest gastrointestinal absorption can be expected from TZS-34 and TCF-3a, and lowest from TLK-13
and NZ-97 (Figure 1). High membrane retention observed for compounds TEL-28 (72%) and TAZ-2b (30 %) might be a
reason for lower permeability than expected based on their lipophilicity.
PB  - MuTaLig COST ACTION CA15135
C3  - Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts
T1  - Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique
SP  - 41
EP  - 41
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5460
ER  - 

@conference{
author = "Dobričić, Vladimir and Marodi, Marko and Marković, Bojan and Tomašič, Tihomir and Zidar, Nace and Peterlin Mašič, Lucija and Ilaš, Janez and Kikelj, Danijel",
year = "2020",
abstract = "In this study, estimation of gastrointestinal absorption of thirteen selected dual DNA gyrase and topoisomerase IV
inhibitors was carried out using PAMPA test. Diffusion through artificial membrane, consisting of egg lecithin solution
in dodecane (first PAMPA model) and a mixture of hexadecane and hexane (second PAMPA model), was monitored
[1,2]. The starting solutions (pH 5.5) and the acceptor medium (pH 7.4) were prepared to contain 2% dimethyl
sulfoxide. Concentrations of tested compounds in starting solutions, donor and acceptor medium after incubation
were measured using LC-MS/MS method. Permeability coefficients were calculated and good correlation was
observed between results obtained using these two PAMPA models. Subsequently, the hexadecane/hexane model
was selected for the evaluation of gastrointestinal absorption of the remaining ten compounds.
Derivatives with the highest permeability in hexadecane/hexane model were TZS-34 and TCF-3a (logPe: -5.37 and
-4.93, respectively) whereas TLK-13 and NZ-97 had the lowest permeability (logPe: -9.91 and -9.85, respectively).
Therefore, the highest gastrointestinal absorption can be expected from TZS-34 and TCF-3a, and lowest from TLK-13
and NZ-97 (Figure 1). High membrane retention observed for compounds TEL-28 (72%) and TAZ-2b (30 %) might be a
reason for lower permeability than expected based on their lipophilicity.",
publisher = "MuTaLig COST ACTION CA15135",
journal = "Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts",
title = "Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique",
pages = "41-41",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5460"
}

Dobričić, V., Marodi, M., Marković, B., Tomašič, T., Zidar, N., Peterlin Mašič, L., Ilaš, J.,& Kikelj, D.. (2020). Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique. in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts
MuTaLig COST ACTION CA15135., 41-41.
https://hdl.handle.net/21.15107/rcub_farfar_5460

Dobričić V, Marodi M, Marković B, Tomašič T, Zidar N, Peterlin Mašič L, Ilaš J, Kikelj D. Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique. in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts. 2020;:41-41.
https://hdl.handle.net/21.15107/rcub_farfar_5460 .

Dobričić, Vladimir, Marodi, Marko, Marković, Bojan, Tomašič, Tihomir, Zidar, Nace, Peterlin Mašič, Lucija, Ilaš, Janez, Kikelj, Danijel, "Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique" in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts (2020):41-41,
https://hdl.handle.net/21.15107/rcub_farfar_5460 .

TY  - JOUR
AU  - Homšek, Ana
AU  - Marković, Bojan
AU  - Bogavac-Stanojević, Nataša
AU  - Vladimirov, Sote
AU  - Karljiković-Rajić, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4833
AB  - The application assessment of different programs was performed with equivalence tests for method transfer pro second-order derivative spectrophotometry. The digital second-order derivative spectra were calculated on different instruments; GBC Scientific Equipment Cintra 20 (Cintral v.2.6 and Spectral v.1.70 software programs) and Thermo Scientific Evolution 300 (VISIONPro software) were analyzed using the amplitude A/B ratio (A = 2D265,263; B = 2D263,261). Amplitude A/B ratio is the resolution parameter for derivative spectrophotometry prescribed in European Pharmacopoeia. The obtained values for A/B ratio were either very similar or significantly different among programs: 0.669 (Cintral v.2.6), 0.549 (Spectral v.1.70), 0.556 (medium indirect VISIONPro), 0.557 (one-step Savitzky–Golay 7 VISIONPro), 0.689 (two-step Savitzky–Golay 7 VISIONPro). Method transfer was possible between Spectral v.1.70 and VISIONPro (medium indirect and one-step Savitzky–Golay 7), but the values obtained in Cintral v.2.6 were not comparable to the other programs. The absorbance data exported from both instruments were additionally calculated in OriginPro8 which provided almost the same mean A/B values (0.627 Cintral v.2.6; 0.624 VISIONPro), confirming that the two instruments recorded the same zero-order spectra. The calculation of resolution parameter could be used for verification of program comparison, which would enable transfer between sender and receiver laboratory. The accordance between program algorithms was confirmed when acceptable differences for values of resolution parameter (A/B ratios) were achieved.
PB  - SAGE Publications
T2  - Applied Spectroscopy
T1  - Method Transfer Evaluation for Digital Derivative Spectrophotometry Through its Resolution Parameter Comparison of Different Computer Programs
VL  - 74
IS  - 5
SP  - 525
EP  - 535
DO  - 10.1177/0003702819889374
ER  - 

@article{
author = "Homšek, Ana and Marković, Bojan and Bogavac-Stanojević, Nataša and Vladimirov, Sote and Karljiković-Rajić, Katarina",
year = "2020",
abstract = "The application assessment of different programs was performed with equivalence tests for method transfer pro second-order derivative spectrophotometry. The digital second-order derivative spectra were calculated on different instruments; GBC Scientific Equipment Cintra 20 (Cintral v.2.6 and Spectral v.1.70 software programs) and Thermo Scientific Evolution 300 (VISIONPro software) were analyzed using the amplitude A/B ratio (A = 2D265,263; B = 2D263,261). Amplitude A/B ratio is the resolution parameter for derivative spectrophotometry prescribed in European Pharmacopoeia. The obtained values for A/B ratio were either very similar or significantly different among programs: 0.669 (Cintral v.2.6), 0.549 (Spectral v.1.70), 0.556 (medium indirect VISIONPro), 0.557 (one-step Savitzky–Golay 7 VISIONPro), 0.689 (two-step Savitzky–Golay 7 VISIONPro). Method transfer was possible between Spectral v.1.70 and VISIONPro (medium indirect and one-step Savitzky–Golay 7), but the values obtained in Cintral v.2.6 were not comparable to the other programs. The absorbance data exported from both instruments were additionally calculated in OriginPro8 which provided almost the same mean A/B values (0.627 Cintral v.2.6; 0.624 VISIONPro), confirming that the two instruments recorded the same zero-order spectra. The calculation of resolution parameter could be used for verification of program comparison, which would enable transfer between sender and receiver laboratory. The accordance between program algorithms was confirmed when acceptable differences for values of resolution parameter (A/B ratios) were achieved.",
publisher = "SAGE Publications",
journal = "Applied Spectroscopy",
title = "Method Transfer Evaluation for Digital Derivative Spectrophotometry Through its Resolution Parameter Comparison of Different Computer Programs",
volume = "74",
number = "5",
pages = "525-535",
doi = "10.1177/0003702819889374"
}

Homšek, A., Marković, B., Bogavac-Stanojević, N., Vladimirov, S.,& Karljiković-Rajić, K.. (2020). Method Transfer Evaluation for Digital Derivative Spectrophotometry Through its Resolution Parameter Comparison of Different Computer Programs. in Applied Spectroscopy
SAGE Publications., 74(5), 525-535.
https://doi.org/10.1177/0003702819889374

Homšek A, Marković B, Bogavac-Stanojević N, Vladimirov S, Karljiković-Rajić K. Method Transfer Evaluation for Digital Derivative Spectrophotometry Through its Resolution Parameter Comparison of Different Computer Programs. in Applied Spectroscopy. 2020;74(5):525-535.
doi:10.1177/0003702819889374 .

Homšek, Ana, Marković, Bojan, Bogavac-Stanojević, Nataša, Vladimirov, Sote, Karljiković-Rajić, Katarina, "Method Transfer Evaluation for Digital Derivative Spectrophotometry Through its Resolution Parameter Comparison of Different Computer Programs" in Applied Spectroscopy, 74, no. 5 (2020):525-535,
https://doi.org/10.1177/0003702819889374 . .

TY  - JOUR
AU  - Nikolić, Ines
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Ranđelovic, Danijela
AU  - Marković, Bojan
AU  - Lunter, Dominique Jasmin
AU  - Kremenović, Aleksandar
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3711
AB  - As the number of poorly soluble drugs is increasing, nanocrystals have become very interesting due to wide range of application possibilities. Curcuminwas used as a model active ingredient in this work. Even though it has many proven positive effects, due to its physicochemical issues, its possibilities have not been fully exploited. The goal of this work was to select optimal conditions for a top-down method for curcumin nanosuspension production, and to perform their comprehensive characterization applying complementary methodologies: dynamic light scattering, polarization and atomic force microscopy, thermal analysis, X-ray powder diffraction, antioxidant activity evaluation, release kinetics assessment, and screening of potential biological effects applying cell viability assays on normal human lung fibroblasts, human melanoma and human adenomacarcinoma cells. After 30 min of milling, nanosuspensions stabilized by polysorbate 80 and by its combinations with sucrose palmitate showed good stability, while curcumin crystal structure was unaltered. Obtained nanocrystals were well defined, with average diameter 120-170 nm and PDI of about 0.25, zeta potential was below -30 mV and pH~5 for all formulations. Nanodispersions exhibited high antioxidant potential and improved dissolution rate compared to the corresponding coarse dispersions. Although curcumin nanodispersions exhibited significant antiproliferative effect to each cancer cell line, the highest effect was towards adenocarcinoma cells.
PB  - Walter de Gruyter GmbH
T2  - Reviews on Advanced Materials Science
T1  - Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals
VL  - 59
IS  - 1
SP  - 406
EP  - 424
DO  - 10.1515/rams-2020-0043
DO  - 2-s2.0-85092928784
ER  - 

@article{
author = "Nikolić, Ines and Antić-Stanković, Jelena and Božić, Dragana and Ranđelovic, Danijela and Marković, Bojan and Lunter, Dominique Jasmin and Kremenović, Aleksandar and Savić, Miroslav and Savić, Snežana",
year = "2020",
abstract = "As the number of poorly soluble drugs is increasing, nanocrystals have become very interesting due to wide range of application possibilities. Curcuminwas used as a model active ingredient in this work. Even though it has many proven positive effects, due to its physicochemical issues, its possibilities have not been fully exploited. The goal of this work was to select optimal conditions for a top-down method for curcumin nanosuspension production, and to perform their comprehensive characterization applying complementary methodologies: dynamic light scattering, polarization and atomic force microscopy, thermal analysis, X-ray powder diffraction, antioxidant activity evaluation, release kinetics assessment, and screening of potential biological effects applying cell viability assays on normal human lung fibroblasts, human melanoma and human adenomacarcinoma cells. After 30 min of milling, nanosuspensions stabilized by polysorbate 80 and by its combinations with sucrose palmitate showed good stability, while curcumin crystal structure was unaltered. Obtained nanocrystals were well defined, with average diameter 120-170 nm and PDI of about 0.25, zeta potential was below -30 mV and pH~5 for all formulations. Nanodispersions exhibited high antioxidant potential and improved dissolution rate compared to the corresponding coarse dispersions. Although curcumin nanodispersions exhibited significant antiproliferative effect to each cancer cell line, the highest effect was towards adenocarcinoma cells.",
publisher = "Walter de Gruyter GmbH",
journal = "Reviews on Advanced Materials Science",
title = "Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals",
volume = "59",
number = "1",
pages = "406-424",
doi = "10.1515/rams-2020-0043, 2-s2.0-85092928784"
}

Nikolić, I., Antić-Stanković, J., Božić, D., Ranđelovic, D., Marković, B., Lunter, D. J., Kremenović, A., Savić, M.,& Savić, S.. (2020). Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals. in Reviews on Advanced Materials Science
Walter de Gruyter GmbH., 59(1), 406-424.
https://doi.org/10.1515/rams-2020-0043

Nikolić I, Antić-Stanković J, Božić D, Ranđelovic D, Marković B, Lunter DJ, Kremenović A, Savić M, Savić S. Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals. in Reviews on Advanced Materials Science. 2020;59(1):406-424.
doi:10.1515/rams-2020-0043 .

Nikolić, Ines, Antić-Stanković, Jelena, Božić, Dragana, Ranđelovic, Danijela, Marković, Bojan, Lunter, Dominique Jasmin, Kremenović, Aleksandar, Savić, Miroslav, Savić, Snežana, "Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals" in Reviews on Advanced Materials Science, 59, no. 1 (2020):406-424,
https://doi.org/10.1515/rams-2020-0043 . .

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 . .