TY  - JOUR
AU  - Gledović, Ana
AU  - Janošević Ležaić, Aleksandra
AU  - Nikolić, Ines
AU  - Tasić-Kostov, Marija Z.
AU  - Antić-Stanković, Jelena
AU  - Krstonošić, Veljko S.
AU  - Randjelović, Danijela
AU  - Božić, Dragana
AU  - Ilić, Dušan
AU  - Tamburić, Slobodanka D.
AU  - Savić, Snežana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4243
AB  - This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions
based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO
and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions
were obtained via phase inversion composition (PIC) method at room temperature by dilution of
microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic,
rheological and differential scanning calorimetry (DSC) investigations. The results have shown that
the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from
red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet
size (Z-ave: 50 to 70 nm, PDI value _ 0.1). The highest antioxidant activity (~92% inhibition of the
DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic
antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased
the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal
human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles
and significant improvement in skin hydration during 2 h after application for all nanoemulsions.
Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red
raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin
protection and hydration.
PB  - MDPI
T2  - Nanomaterials
T1  - Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance
VL  - 11
IS  - 1
SP  - 1
EP  - 21
DO  - 10.3390/nano11010217
ER  - 

@article{
author = "Gledović, Ana and Janošević Ležaić, Aleksandra and Nikolić, Ines and Tasić-Kostov, Marija Z. and Antić-Stanković, Jelena and Krstonošić, Veljko S. and Randjelović, Danijela and Božić, Dragana and Ilić, Dušan and Tamburić, Slobodanka D. and Savić, Snežana",
year = "2021",
abstract = "This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions
based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO
and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions
were obtained via phase inversion composition (PIC) method at room temperature by dilution of
microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic,
rheological and differential scanning calorimetry (DSC) investigations. The results have shown that
the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from
red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet
size (Z-ave: 50 to 70 nm, PDI value _ 0.1). The highest antioxidant activity (~92% inhibition of the
DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic
antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased
the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal
human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles
and significant improvement in skin hydration during 2 h after application for all nanoemulsions.
Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red
raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin
protection and hydration.",
publisher = "MDPI",
journal = "Nanomaterials",
title = "Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance",
volume = "11",
number = "1",
pages = "1-21",
doi = "10.3390/nano11010217"
}

Gledović, A., Janošević Ležaić, A., Nikolić, I., Tasić-Kostov, M. Z., Antić-Stanković, J., Krstonošić, V. S., Randjelović, D., Božić, D., Ilić, D., Tamburić, S. D.,& Savić, S.. (2021). Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance. in Nanomaterials
MDPI., 11(1), 1-21.
https://doi.org/10.3390/nano11010217

Gledović A, Janošević Ležaić A, Nikolić I, Tasić-Kostov MZ, Antić-Stanković J, Krstonošić VS, Randjelović D, Božić D, Ilić D, Tamburić SD, Savić S. Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance. in Nanomaterials. 2021;11(1):1-21.
doi:10.3390/nano11010217 .

Gledović, Ana, Janošević Ležaić, Aleksandra, Nikolić, Ines, Tasić-Kostov, Marija Z., Antić-Stanković, Jelena, Krstonošić, Veljko S., Randjelović, Danijela, Božić, Dragana, Ilić, Dušan, Tamburić, Slobodanka D., Savić, Snežana, "Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance" in Nanomaterials, 11, no. 1 (2021):1-21,
https://doi.org/10.3390/nano11010217 . .

TY  - JOUR
AU  - Ðoković, Jelena B.
AU  - Savić, Sanela M.
AU  - Mitrović, Jelena R.
AU  - Nikolić, Ines
AU  - Marković, Bojan D.
AU  - Randjelović, Danijela
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Cekić, Nebojša D.
AU  - Stevanović, Vladimir
AU  - Batinić, Bojan
AU  - Aranđelović, Jovana
AU  - Savić, Miroslav M.
AU  - Savić, Snežana D.
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4822
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
IS  - 7991
DO  - 10.3390/ijms22157991
ER  - 

@article{
author = "Ðoković, Jelena B. and Savić, Sanela M. and Mitrović, Jelena R. and Nikolić, Ines and Marković, Bojan D. and Randjelović, Danijela and Antić-Stanković, Jelena and Božić, Dragana and Cekić, Nebojša D. and Stevanović, Vladimir and Batinić, Bojan and Aranđelović, Jovana and Savić, Miroslav M. and Savić, Snežana D.",
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, 7991",
doi = "10.3390/ijms22157991"
}

Ðoković, J. B., Savić, S. M., Mitrović, J. R., Nikolić, I., Marković, B. D., Randjelović, D., Antić-Stanković, J., Božić, D., Cekić, N. D., Stevanović, V., Batinić, B., Aranđelović, J., Savić, M. M.,& Savić, S. D.. (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

Ðoković JB, Savić SM, Mitrović JR, Nikolić I, Marković BD, Randjelović D, Antić-Stanković J, Božić D, Cekić ND, Stevanović V, Batinić B, Aranđelović J, Savić MM, Savić SD. 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 .

Ðoković, Jelena B., Savić, Sanela M., Mitrović, Jelena R., Nikolić, Ines, Marković, Bojan D., Randjelović, Danijela, Antić-Stanković, Jelena, Božić, Dragana, Cekić, Nebojša D., Stevanović, Vladimir, Batinić, Bojan, Aranđelović, Jovana, Savić, Miroslav M., Savić, Snežana D., "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  - Nikolić, Ines
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Randjelović, Danijela
AU  - Marković, Bojan D.
AU  - Lunter, Dominique Jasmin
AU  - Kremenović, Aleksandar
AU  - Savić, Miroslav M.
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3711
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3720
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
ER  - 

@article{
author = "Nikolić, Ines and Antić-Stanković, Jelena and Božić, Dragana and Randjelović, Danijela and Marković, Bojan D. and Lunter, Dominique Jasmin and Kremenović, Aleksandar and Savić, Miroslav M. 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"
}

Nikolić, I., Antić-Stanković, J., Božić, D., Randjelović, D., Marković, B. D., Lunter, D. J., Kremenović, A., Savić, M. 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, Randjelović D, Marković BD, Lunter DJ, Kremenović A, Savić MM, 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, Randjelović, Danijela, Marković, Bojan D., Lunter, Dominique Jasmin, Kremenović, Aleksandar, Savić, Miroslav M., 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  - Dmitrović, Slavica
AU  - Škorić, Marijana
AU  - Boljević, Jelena
AU  - Aničić, Neda
AU  - Božić, Dragana
AU  - Mišić, Danijela
AU  - Filipović, Vuk
AU  - Opsenica, Dejan
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1892
AB  - The presented study aimed to investigate the elicitation possibility for the production of main secondary metabolites in Nepeta cataria L. and N. pannonica L. plants, by exposing them to synthetic compounds belonging to tetraoxanes and thiophenes group. The effect of DO63 (1,2,4,5-tetraoxane) and DOVF15 (2,5-diphenylthiophene) on the production of cis-trans-nepetalactone (NL) and rosmarinic acid (RA) in two Nepeta species, was investigated in shoots grown on the culture medium with the addition of synthetic compounds in the concentrations ranging from 0.1 to 2 mg L-1. The content of targeted metabolites in tested in vitro shoots depended on the type and concentration of applied synthetic compounds. Application of DO63 in the concentration range 0.1-1 mg L-1 affected only NL production in both Nepeta species resulting in its increased content, while production of RA was not influenced in the treated shoots. Addition of DOVF15 caused decreased RA content in N. pannonica shoots and an increase in N. cataria shoots, whereas NL production was not affected. The presented results reveal the possibility of DO63 and DOVF15 application for the elicitation of the main secondary metabolites production in species from the genus Nepeta.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species
VL  - 81
IS  - 9
SP  - 999
EP  - 1012
DO  - 10.2298/JSC160226054D
ER  - 

@article{
author = "Dmitrović, Slavica and Škorić, Marijana and Boljević, Jelena and Aničić, Neda and Božić, Dragana and Mišić, Danijela and Filipović, Vuk and Opsenica, Dejan",
year = "2016",
abstract = "The presented study aimed to investigate the elicitation possibility for the production of main secondary metabolites in Nepeta cataria L. and N. pannonica L. plants, by exposing them to synthetic compounds belonging to tetraoxanes and thiophenes group. The effect of DO63 (1,2,4,5-tetraoxane) and DOVF15 (2,5-diphenylthiophene) on the production of cis-trans-nepetalactone (NL) and rosmarinic acid (RA) in two Nepeta species, was investigated in shoots grown on the culture medium with the addition of synthetic compounds in the concentrations ranging from 0.1 to 2 mg L-1. The content of targeted metabolites in tested in vitro shoots depended on the type and concentration of applied synthetic compounds. Application of DO63 in the concentration range 0.1-1 mg L-1 affected only NL production in both Nepeta species resulting in its increased content, while production of RA was not influenced in the treated shoots. Addition of DOVF15 caused decreased RA content in N. pannonica shoots and an increase in N. cataria shoots, whereas NL production was not affected. The presented results reveal the possibility of DO63 and DOVF15 application for the elicitation of the main secondary metabolites production in species from the genus Nepeta.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species",
volume = "81",
number = "9",
pages = "999-1012",
doi = "10.2298/JSC160226054D"
}

Dmitrović, S., Škorić, M., Boljević, J., Aničić, N., Božić, D., Mišić, D., Filipović, V.,& Opsenica, D.. (2016). Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 81(9), 999-1012.
https://doi.org/10.2298/JSC160226054D

Dmitrović S, Škorić M, Boljević J, Aničić N, Božić D, Mišić D, Filipović V, Opsenica D. Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species. in Journal of the Serbian Chemical Society. 2016;81(9):999-1012.
doi:10.2298/JSC160226054D .

Dmitrović, Slavica, Škorić, Marijana, Boljević, Jelena, Aničić, Neda, Božić, Dragana, Mišić, Danijela, Filipović, Vuk, Opsenica, Dejan, "Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species" in Journal of the Serbian Chemical Society, 81, no. 9 (2016):999-1012,
https://doi.org/10.2298/JSC160226054D . .