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Kojić, Vesna V.

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Author's Bibliography

Mg/Cu co-substituted hydroxyapatite – Biocompatibility, mechanical properties and antimicrobial activity

Veljović, Đorđe; Matić, Tamara; Stamenić, Tanja; Kojić, Vesna; Dimitrijević Branković, Suzana; Lukić, Miodrag J.; Jevtić, Sanja; Radovanović, Željko; Petrović, Rada; Janaćković, Đorđe

(Elsevier, 2019)

TY  - JOUR
AU  - Veljović, Đorđe
AU  - Matić, Tamara
AU  - Stamenić, Tanja
AU  - Kojić, Vesna
AU  - Dimitrijević Branković, Suzana
AU  - Lukić, Miodrag J.
AU  - Jevtić, Sanja
AU  - Radovanović, Željko
AU  - Petrović, Rada
AU  - Janaćković, Đorđe
PY  - 2019
UR  - http://www.sciencedirect.com/science/article/pii/S0272884219320413
UR  - http://dais.sanu.ac.rs/123456789/6504
AB  - The aim of this study was to improve the mechanical properties and to optimize antimicrobial activity of hydroxyapatite (HAP) by simultaneous doping with Mg and Cu ions in order to obtain material that would be able to assist in the bone/tooth healing process, prevent post-implementation infections and provide satisfying values of hardness and fracture toughness for biomedical application. Ion doping was done during the hydrothermal synthesis of HAP powders, whereby the content of Mg ions in the starting solution was varied between 1-20 mol. % with regard to Ca ions, while the amount of Cu ions was kept constant at 0.4 mol. %. The green compacts were sintered for 2 h at temperatures ranging 750–1200 °C depending on the Mg content, chosen in agreement with dilatometry results. Presence of Mg ions was found to favour transition from HAP to β−tricalcium phosphate phase (β−TCP), which enabled formation of biphasic HAP/β−TCP and pure β−TCP phase at 160 °C during hydrothermal synthesis. In vitro investigation of antimicrobial activity against Escherichia coli, Staphylococcus aureus and Enterococcus faecalis showed satisfactory antimicrobial activity. MTT assay performed on MRC-5 and L929 cell lines showed excellent cytocompatibility and cell proliferation. Maximum hardness by Vickers and fracture toughness values, 4.96 GPa and 1.75 MPa m1/2 respectively, were obtained upon addition of 5 mol. % Mg, as a consequence of the lowest grain size and porosity, as well as the highest densification rate. This is, to the best of our knowledge, the highest fracture toughness for HAP or β-TCP ceramics reported thus far.
PB  - Elsevier
T2  - Ceramics International
T1  - Mg/Cu co-substituted hydroxyapatite – Biocompatibility, mechanical properties and antimicrobial activity
SP  - 22029
SP  - 22039
VL  - 45
IS  - 17, Part A
DO  - 10.1016/j.ceramint.2019.07.219
ER  - 
@article{
author = "Veljović, Đorđe and Matić, Tamara and Stamenić, Tanja and Kojić, Vesna and Dimitrijević Branković, Suzana and Lukić, Miodrag J. and Jevtić, Sanja and Radovanović, Željko and Petrović, Rada and Janaćković, Đorđe",
year = "2019",
url = "http://www.sciencedirect.com/science/article/pii/S0272884219320413, http://dais.sanu.ac.rs/123456789/6504",
abstract = "The aim of this study was to improve the mechanical properties and to optimize antimicrobial activity of hydroxyapatite (HAP) by simultaneous doping with Mg and Cu ions in order to obtain material that would be able to assist in the bone/tooth healing process, prevent post-implementation infections and provide satisfying values of hardness and fracture toughness for biomedical application. Ion doping was done during the hydrothermal synthesis of HAP powders, whereby the content of Mg ions in the starting solution was varied between 1-20 mol. % with regard to Ca ions, while the amount of Cu ions was kept constant at 0.4 mol. %. The green compacts were sintered for 2 h at temperatures ranging 750–1200 °C depending on the Mg content, chosen in agreement with dilatometry results. Presence of Mg ions was found to favour transition from HAP to β−tricalcium phosphate phase (β−TCP), which enabled formation of biphasic HAP/β−TCP and pure β−TCP phase at 160 °C during hydrothermal synthesis. In vitro investigation of antimicrobial activity against Escherichia coli, Staphylococcus aureus and Enterococcus faecalis showed satisfactory antimicrobial activity. MTT assay performed on MRC-5 and L929 cell lines showed excellent cytocompatibility and cell proliferation. Maximum hardness by Vickers and fracture toughness values, 4.96 GPa and 1.75 MPa m1/2 respectively, were obtained upon addition of 5 mol. % Mg, as a consequence of the lowest grain size and porosity, as well as the highest densification rate. This is, to the best of our knowledge, the highest fracture toughness for HAP or β-TCP ceramics reported thus far.",
publisher = "Elsevier",
journal = "Ceramics International",
title = "Mg/Cu co-substituted hydroxyapatite – Biocompatibility, mechanical properties and antimicrobial activity",
pages = "22029-22039",
volume = "45",
number = "17, Part A",
doi = "10.1016/j.ceramint.2019.07.219"
}
8
6
8

Mg/Cu co-substituted hydroxyapatite – Biocompatibility, mechanical properties and antimicrobial activity

Veljović, Đorđe; Matić, Tamara; Stamenić, Tanja; Kojić, Vesna; Dimitrijević Branković, Suzana; Lukić, Miodrag J.; Jevtić, Sanja; Radovanović, Željko; Petrović, Rada; Janaćković, Đorđe

(Elsevier, 2019)

TY  - JOUR
AU  - Veljović, Đorđe
AU  - Matić, Tamara
AU  - Stamenić, Tanja
AU  - Kojić, Vesna
AU  - Dimitrijević Branković, Suzana
AU  - Lukić, Miodrag J.
AU  - Jevtić, Sanja
AU  - Radovanović, Željko
AU  - Petrović, Rada
AU  - Janaćković, Đorđe
PY  - 2019
UR  - http://www.sciencedirect.com/science/article/pii/S0272884219320413
UR  - http://dais.sanu.ac.rs/123456789/6948
AB  - The aim of this study was to improve the mechanical properties and to optimize antimicrobial activity of hydroxyapatite (HAP) by simultaneous doping with Mg and Cu ions in order to obtain material that would be able to assist in the bone/tooth healing process, prevent post-implementation infections and provide satisfying values of hardness and fracture toughness for biomedical application. Ion doping was done during the hydrothermal synthesis of HAP powders, whereby the content of Mg ions in the starting solution was varied between 1-20 mol. % with regard to Ca ions, while the amount of Cu ions was kept constant at 0.4 mol. %. The green compacts were sintered for 2 h at temperatures ranging 750–1200 °C depending on the Mg content, chosen in agreement with dilatometry results. Presence of Mg ions was found to favour transition from HAP to β−tricalcium phosphate phase (β−TCP), which enabled formation of biphasic HAP/β−TCP and pure β−TCP phase at 160 °C during hydrothermal synthesis. In vitro investigation of antimicrobial activity against Escherichia coli, Staphylococcus aureus and Enterococcus faecalis showed satisfactory antimicrobial activity. MTT assay performed on MRC-5 and L929 cell lines showed excellent cytocompatibility and cell proliferation. Maximum hardness by Vickers and fracture toughness values, 4.96 GPa and 1.75 MPa m1/2 respectively, were obtained upon addition of 5 mol. % Mg, as a consequence of the lowest grain size and porosity, as well as the highest densification rate. This is, to the best of our knowledge, the highest fracture toughness for HAP or β-TCP ceramics reported thus far.
PB  - Elsevier
T2  - Ceramics International
T1  - Mg/Cu co-substituted hydroxyapatite – Biocompatibility, mechanical properties and antimicrobial activity
SP  - 22029
SP  - 22039
VL  - 45
IS  - 17, Part A
DO  - 10.1016/j.ceramint.2019.07.219
ER  - 
@article{
author = "Veljović, Đorđe and Matić, Tamara and Stamenić, Tanja and Kojić, Vesna and Dimitrijević Branković, Suzana and Lukić, Miodrag J. and Jevtić, Sanja and Radovanović, Željko and Petrović, Rada and Janaćković, Đorđe",
year = "2019",
url = "http://www.sciencedirect.com/science/article/pii/S0272884219320413, http://dais.sanu.ac.rs/123456789/6948",
abstract = "The aim of this study was to improve the mechanical properties and to optimize antimicrobial activity of hydroxyapatite (HAP) by simultaneous doping with Mg and Cu ions in order to obtain material that would be able to assist in the bone/tooth healing process, prevent post-implementation infections and provide satisfying values of hardness and fracture toughness for biomedical application. Ion doping was done during the hydrothermal synthesis of HAP powders, whereby the content of Mg ions in the starting solution was varied between 1-20 mol. % with regard to Ca ions, while the amount of Cu ions was kept constant at 0.4 mol. %. The green compacts were sintered for 2 h at temperatures ranging 750–1200 °C depending on the Mg content, chosen in agreement with dilatometry results. Presence of Mg ions was found to favour transition from HAP to β−tricalcium phosphate phase (β−TCP), which enabled formation of biphasic HAP/β−TCP and pure β−TCP phase at 160 °C during hydrothermal synthesis. In vitro investigation of antimicrobial activity against Escherichia coli, Staphylococcus aureus and Enterococcus faecalis showed satisfactory antimicrobial activity. MTT assay performed on MRC-5 and L929 cell lines showed excellent cytocompatibility and cell proliferation. Maximum hardness by Vickers and fracture toughness values, 4.96 GPa and 1.75 MPa m1/2 respectively, were obtained upon addition of 5 mol. % Mg, as a consequence of the lowest grain size and porosity, as well as the highest densification rate. This is, to the best of our knowledge, the highest fracture toughness for HAP or β-TCP ceramics reported thus far.",
publisher = "Elsevier",
journal = "Ceramics International",
title = "Mg/Cu co-substituted hydroxyapatite – Biocompatibility, mechanical properties and antimicrobial activity",
pages = "22029-22039",
volume = "45",
number = "17, Part A",
doi = "10.1016/j.ceramint.2019.07.219"
}
8
6
8

Synthesis and characterization of bioactive glass doped with lithium and strontium ions

Veljović, Đorđe; Radovanović, Željko; Rogan, Jelena; Dapčević, Aleksandra; Dimitrijević, Suzana; Dimitrijević Branković, Suzana; Kojić, Vesna; Janaćković, Đorđe

(Belgrade : Institute of Technical Sciences of SASA, 2018)

TY  - CONF
AU  - Veljović, Đorđe
AU  - Radovanović, Željko
AU  - Rogan, Jelena
AU  - Dapčević, Aleksandra
AU  - Dimitrijević, Suzana
AU  - Dimitrijević Branković, Suzana
AU  - Kojić, Vesna
AU  - Janaćković, Đorđe
PY  - 2018
UR  - http://dais.sanu.ac.rs/123456789/4718
AB  - Bioactive glasses have been used for over three decades in biomedical applications owing to high bioactivity, biocompatibility, as well as the possibility to stimulate regeneration of the bone. The aim of this work was to synthesized bioactive glasses, which contain lithium and strontium, by commercial method melting-quenching, as well as determining the properties, affected by mentioned ions. Differential thermal/thermogravimetric analysis, particle size distribution, energy-dispersive X-ray spectroscopy, inductively coupled plasma optical emission spectrometry, evaluation of the antimicrobial activity, in vitro bioactivity and biocompatibility test and scanning electron microscopy were used for characterization. The results showed that glass transition and crystallization temperatures are decreasing with addition of lithium and strontium ions. Furthermore, the samples showed high inhibition rate of Escherichia coli growth, as well as high bioactivity and biocompatibility. The crystal apatite layer, formed on the surface of synthesized glasses after seven days in simulated body fluid, differs in shape, size and interconnection of the glass particles, which depends on concentration of lithium and strontium ions.
PB  - Belgrade : Institute of Technical Sciences of SASA
C3  - Program and the Book of Abstracts / Seventeenth Young Researchers' Conference Materials Sciences and Engineering, December 5-7, 2018, Belgrade, Serbia
T1  - Synthesis and characterization of bioactive glass doped with lithium and strontium ions
SP  - 20
EP  - 20
ER  - 
@conference{
author = "Veljović, Đorđe and Radovanović, Željko and Rogan, Jelena and Dapčević, Aleksandra and Dimitrijević, Suzana and Dimitrijević Branković, Suzana and Kojić, Vesna and Janaćković, Đorđe",
year = "2018",
url = "http://dais.sanu.ac.rs/123456789/4718",
abstract = "Bioactive glasses have been used for over three decades in biomedical applications owing to high bioactivity, biocompatibility, as well as the possibility to stimulate regeneration of the bone. The aim of this work was to synthesized bioactive glasses, which contain lithium and strontium, by commercial method melting-quenching, as well as determining the properties, affected by mentioned ions. Differential thermal/thermogravimetric analysis, particle size distribution, energy-dispersive X-ray spectroscopy, inductively coupled plasma optical emission spectrometry, evaluation of the antimicrobial activity, in vitro bioactivity and biocompatibility test and scanning electron microscopy were used for characterization. The results showed that glass transition and crystallization temperatures are decreasing with addition of lithium and strontium ions. Furthermore, the samples showed high inhibition rate of Escherichia coli growth, as well as high bioactivity and biocompatibility. The crystal apatite layer, formed on the surface of synthesized glasses after seven days in simulated body fluid, differs in shape, size and interconnection of the glass particles, which depends on concentration of lithium and strontium ions.",
publisher = "Belgrade : Institute of Technical Sciences of SASA",
journal = "Program and the Book of Abstracts / Seventeenth Young Researchers' Conference Materials Sciences and Engineering, December 5-7, 2018, Belgrade, Serbia",
title = "Synthesis and characterization of bioactive glass doped with lithium and strontium ions",
pages = "20-20"
}

Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells

Ignjatović, Nenad; Sakač, Marija; Kuzminac, Ivana; Kojić, Vesna; Marković, Smilja; Vasiljević Radović, Dana; Wu, Victoria; Uskoković, Vuk; Uskoković, Dragan

(Royal Society of Chemistry, 2018)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna
AU  - Marković, Smilja
AU  - Vasiljević Radović, Dana
AU  - Wu, Victoria
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2018
UR  - http://dais.sanu.ac.rs/123456789/4066
AB  - Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells
SP  - 6957
EP  - 6968
VL  - 6
DO  - 10.1039/C8TB01995A
ER  - 
@article{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna and Marković, Smilja and Vasiljević Radović, Dana and Wu, Victoria and Uskoković, Vuk and Uskoković, Dragan",
year = "2018",
url = "http://dais.sanu.ac.rs/123456789/4066",
abstract = "Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells",
pages = "6957-6968",
volume = "6",
doi = "10.1039/C8TB01995A"
}
3
13
10
12

The effect of the androstane lung cancer inhibitor content on the cell-selective toxicity of hydroxyapatite-chitosan-PLGA nanocomposites

Ignjatović, Nenad; Penov Gaši, Katarina; Ajduković, Jovana; Kojić, Vesna; Marković, Smilja; Uskoković, Dragan

(Elsevier, 2018)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Ajduković, Jovana
AU  - Kojić, Vesna
AU  - Marković, Smilja
AU  - Uskoković, Dragan
PY  - 2018
UR  - http://dais.sanu.ac.rs/123456789/4067
AB  - An androstane (17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (derivative A)) cancer inhibitor was successfully captured in a carrier made of nano-sized hydroxyapatite (HAp) coated with chitosan-PLGA polymer blends (Ch-PLGA). In our previous studies, we demonstrated that it was convenient to use spherical HAp/Ch-PLGA carriers as vehicles to target the lungs following intravenous administration. In this study, we used emulsification and subsequent freeze-drying to load the spherical HAp/Ch-PLGA carriers with varying contents of the derivative A, in order to examine the selective toxicity towards cancerous/healthy lung cells. The XRD and FT-IR techniques confirmed the drug loading process, and the content of the poorly water soluble derivative A was estimated directly via the DSC technique. The particles were spherical in shape with the d50 distribution varying between 167 and 231 nm, whereas the content of the derivative A ranged from 6.5 to 19.3 wt%. Cell-selective cytotoxicity was examined simultaneously on two cell lines: human lung carcinoma (A549 ATCC CCL 185) and human lung fibroblasts (MRC-5 ATCC CCL 171). All particles exhibited nearly three times larger cytotoxicity towards cancer cells (A549) than towards healthy cells (MRC5), where the particles with the derivative A content of 6.5 wt% allowed for the viability of healthy cells >80%. Ninety-six hours after the treatment of cells with particles with different contents of derivative A (after incubation and recovery), recovery was faster in damaged healthy cells than in cancerous cells.
PB  - Elsevier
T2  - Materials Science and Engineering: C
T1  - The effect of the androstane lung cancer inhibitor content on the cell-selective toxicity of hydroxyapatite-chitosan-PLGA nanocomposites
SP  - 371
EP  - 377
VL  - 89
IS  - 1
DO  - 10.1016/j.msec.2018.04.028
ER  - 
@article{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Ajduković, Jovana and Kojić, Vesna and Marković, Smilja and Uskoković, Dragan",
year = "2018",
url = "http://dais.sanu.ac.rs/123456789/4067",
abstract = "An androstane (17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (derivative A)) cancer inhibitor was successfully captured in a carrier made of nano-sized hydroxyapatite (HAp) coated with chitosan-PLGA polymer blends (Ch-PLGA). In our previous studies, we demonstrated that it was convenient to use spherical HAp/Ch-PLGA carriers as vehicles to target the lungs following intravenous administration. In this study, we used emulsification and subsequent freeze-drying to load the spherical HAp/Ch-PLGA carriers with varying contents of the derivative A, in order to examine the selective toxicity towards cancerous/healthy lung cells. The XRD and FT-IR techniques confirmed the drug loading process, and the content of the poorly water soluble derivative A was estimated directly via the DSC technique. The particles were spherical in shape with the d50 distribution varying between 167 and 231 nm, whereas the content of the derivative A ranged from 6.5 to 19.3 wt%. Cell-selective cytotoxicity was examined simultaneously on two cell lines: human lung carcinoma (A549 ATCC CCL 185) and human lung fibroblasts (MRC-5 ATCC CCL 171). All particles exhibited nearly three times larger cytotoxicity towards cancer cells (A549) than towards healthy cells (MRC5), where the particles with the derivative A content of 6.5 wt% allowed for the viability of healthy cells >80%. Ninety-six hours after the treatment of cells with particles with different contents of derivative A (after incubation and recovery), recovery was faster in damaged healthy cells than in cancerous cells.",
publisher = "Elsevier",
journal = "Materials Science and Engineering: C",
title = "The effect of the androstane lung cancer inhibitor content on the cell-selective toxicity of hydroxyapatite-chitosan-PLGA nanocomposites",
pages = "371-377",
volume = "89",
number = "1",
doi = "10.1016/j.msec.2018.04.028"
}
1
2
2

Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells

Ignjatović, Nenad; Sakač, Marija; Kuzminac, Ivana; Kojić, Vesna; Marković, Smilja; Vasiljević Radović, Dana; Wu, Victoria M.; Uskoković, Vuk; Uskoković, Dragan

(Royal Society of Chemistry, 2018)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna
AU  - Marković, Smilja
AU  - Vasiljević Radović, Dana
AU  - Wu, Victoria M.
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2018
UR  - https://pubs.rsc.org/en/content/articlelanding/2018/tb/c8tb01995a
UR  - http://dais.sanu.ac.rs/123456789/4509
AB  - Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells
SP  - 6957
EP  - 696
VL  - 6
DO  - 10.1039/C8TB01995A
ER  - 
@article{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna and Marković, Smilja and Vasiljević Radović, Dana and Wu, Victoria M. and Uskoković, Vuk and Uskoković, Dragan",
year = "2018",
url = "https://pubs.rsc.org/en/content/articlelanding/2018/tb/c8tb01995a, http://dais.sanu.ac.rs/123456789/4509",
abstract = "Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells",
pages = "6957-696",
volume = "6",
doi = "10.1039/C8TB01995A"
}
3
13
10
13

Highly selective anticancer activity of core shell particles based on hydroxyapatite, chitosan lactate and different androstane derivatives

Ignjatović, Nenad; Penov Gaši, Katarina; Ajduković, Jovana; Sakač, Marija; Kuzminac, Ivana; Kojić, Vesna V.; Marković, Smilja; Uskoković, Dragan

(Belgrade : Materials Research Society of Serbia, 2017)

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Ajduković, Jovana
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna V.
AU  - Marković, Smilja
AU  - Uskoković, Dragan
PY  - 2017
UR  - http://dais.sanu.ac.rs/123456789/15442
AB  - Hybrid systems based on nano hydroxyapatites (HAp) are the subject of numerous studies in preventive and regenerative medicine. Special interests are directed towards the creation of a system based on HAp for use in a nano-oncology. The main objective of this research is directed towards the creation of a system with cytotoxic properties towards the cancer cells with the same time, minimum side effects. Carriers base on core shell of HAp/chitosan-poly(D,L)-lactide-coglycolide (PLGA) loaded with androstane-based cancer inhibitor could be seen as promising drug delivery platforms for selective cancer therapies.
In this study we utilize an emulsification process and freeze drying to load the composite particles based on HAp nanocarrier, chitosane (Ch), PLGA and chitosan oligosaccharide lactate (ChOL) with 17β-hydroxy-17α-picolyl-androst-5-en-3β-acetate (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-en (B), a chemotherapeutic derivatives of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormone-dependent cancers (lung, prostate and colon cancer; adeno and cervix carcinoma; etc.).
1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivatives A and B. The thermogravimetric and differential thermal analysis (TGA, DTA) coupled with mass spectrometry was used to qualitatively confirm the drug loading process. FT-IR, XRD, AFM and DSC techniques have confirmed the success of androstane (A and B) loading process in core shell particles base on nano hydroxyapatite. All the synthesized particles were found to be spherical in shape with a uniform size distribution from d50=167 to d50=231 nm. Highly selective anticancer activity was noted towards the human lung carcinoma (A549) by A loaded HAp/Ch-PLGA and towards the human breast adenocarcinoma (MDA-MB-231) by B loaded HAp/ChOL. The obtained results of the DET and MTT tests were in agreement.
PB  - Belgrade : Materials Research Society of Serbia
C3  - Programme and The Book of Abstracts / Nineteenth Annual Conference YUCOMAT 2017, Herceg Novi, September 4-8, 2017
T1  - Highly selective anticancer activity of core shell particles based on hydroxyapatite, chitosan lactate and different androstane derivatives
SP  - 50
EP  - 50
ER  - 
@conference{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Ajduković, Jovana and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna V. and Marković, Smilja and Uskoković, Dragan",
year = "2017",
url = "http://dais.sanu.ac.rs/123456789/15442",
abstract = "Hybrid systems based on nano hydroxyapatites (HAp) are the subject of numerous studies in preventive and regenerative medicine. Special interests are directed towards the creation of a system based on HAp for use in a nano-oncology. The main objective of this research is directed towards the creation of a system with cytotoxic properties towards the cancer cells with the same time, minimum side effects. Carriers base on core shell of HAp/chitosan-poly(D,L)-lactide-coglycolide (PLGA) loaded with androstane-based cancer inhibitor could be seen as promising drug delivery platforms for selective cancer therapies.
In this study we utilize an emulsification process and freeze drying to load the composite particles based on HAp nanocarrier, chitosane (Ch), PLGA and chitosan oligosaccharide lactate (ChOL) with 17β-hydroxy-17α-picolyl-androst-5-en-3β-acetate (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-en (B), a chemotherapeutic derivatives of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormone-dependent cancers (lung, prostate and colon cancer; adeno and cervix carcinoma; etc.).
1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivatives A and B. The thermogravimetric and differential thermal analysis (TGA, DTA) coupled with mass spectrometry was used to qualitatively confirm the drug loading process. FT-IR, XRD, AFM and DSC techniques have confirmed the success of androstane (A and B) loading process in core shell particles base on nano hydroxyapatite. All the synthesized particles were found to be spherical in shape with a uniform size distribution from d50=167 to d50=231 nm. Highly selective anticancer activity was noted towards the human lung carcinoma (A549) by A loaded HAp/Ch-PLGA and towards the human breast adenocarcinoma (MDA-MB-231) by B loaded HAp/ChOL. The obtained results of the DET and MTT tests were in agreement.",
publisher = "Belgrade : Materials Research Society of Serbia",
journal = "Programme and The Book of Abstracts / Nineteenth Annual Conference YUCOMAT 2017, Herceg Novi, September 4-8, 2017",
title = "Highly selective anticancer activity of core shell particles based on hydroxyapatite, chitosan lactate and different androstane derivatives",
pages = "50-50"
}

Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor

Ignjatović, Nenad; Penov Gaši, Katarina; Wu, Victoria; Ajduković, Jovana; Kojić, Vesna; Vasiljević Radović, Dana; Kuzmanović, Maja; Uskoković, Vuk; Uskoković, Dragan

(2016)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna
AU  - Vasiljević Radović, Dana
AU  - Kuzmanović, Maja
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - http://dais.sanu.ac.rs/123456789/15984
AB  - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.
T2  - Colloids and Surfaces B: Biointerfaces
T1  - Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
SP  - 629
EP  - 639
VL  - 148
DO  - 10.1016/j.colsurfb.2016.09.041
ER  - 
@article{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna and Vasiljević Radović, Dana and Kuzmanović, Maja and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
url = "http://dais.sanu.ac.rs/123456789/15984",
abstract = "In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.",
journal = "Colloids and Surfaces B: Biointerfaces",
title = "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor",
pages = "629-639",
volume = "148",
doi = "10.1016/j.colsurfb.2016.09.041"
}
15
15
19

Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor

Ignjatović, Nenad; Penov Gaši, Katarina; Wu, Victoria; Ajduković, Jovana; Kojić, Vesna V.; Vasiljević Radović, Dana; Kuzmanović, Maja; Uskoković, Vuk; Uskoković, Dragan

(Elsevier, 2016)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna V.
AU  - Vasiljević Radović, Dana
AU  - Kuzmanović, Maja
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - http://dais.sanu.ac.rs/123456789/15974
AB  - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50=168nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46±2%), while simultaneously preserving high viability (83±3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.
PB  - Elsevier
T2  - Colloids and Surfaces B: Biointerfaces
T1  - Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
SP  - 629
EP  - 639
VL  - 148
DO  - 10.1016/j.colsurfb.2016.09.041
ER  - 
@article{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna V. and Vasiljević Radović, Dana and Kuzmanović, Maja and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
url = "http://dais.sanu.ac.rs/123456789/15974",
abstract = "In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50=168nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46±2%), while simultaneously preserving high viability (83±3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.",
publisher = "Elsevier",
journal = "Colloids and Surfaces B: Biointerfaces",
title = "Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor",
pages = "629-639",
volume = "148",
doi = "10.1016/j.colsurfb.2016.09.041"
}
15
15
19

Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate

Ignjatović, Nenad; Penov Gaši, Katarina; Wu, Victoria; Ajduković, Jovana; Kojić, Vesna; Vasiljević Radović, Dana; Uskoković, Vuk; Uskoković, Dragan

(Belgrade : Materials Research Society of Serbia, 2016)

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna
AU  - Vasiljević Radović, Dana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - http://dais.sanu.ac.rs/123456789/896
AB  - The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Previously we have shown that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous administration into mice. For this purpose radioactive 125-Iodine (125I), a low energy gamma emitter, was used to develop a novel in situ method for radiolabeling of particles and investigation of their biodistribution. In this study we utilize an emulsification process and freeze drying to load the composite particles based on hydroxyapatite nanocarrier, chitosane and poly(lactic-co-glycolic acid) with 17β- hydroxy-17α-picolyl-androst-5-en-3β-acetate (A), a chemotherapeutic derivative of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormonedependent cancers (adenocarcinoma, prostate cancer, cervix carcinoma, colon cancer, etc.). 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The synthesized particles of A-loaded HAp/Ch-PLGA were found to be spherical in shape with a uniform size distribution of d50=168 nm. The release of A from HAp/Ch-PLGA was sustained, with no burst release or plateauing after three weeks. The obtained results of the DET and MTT tests show that the particles of A-loaded HAp/Ch-PLGA exhibit almost three times higher cytotoxicity towards lung adenocarcinoma cells (A549) than towards healthy cells (MRC5), while at the same time allowing twice as fast recovery of healthy cells. We have also analyzed the period of recovery of healthy, as well as cancer cells, following the treatment with A-loaded HAp/Ch-PLGA. After treatment with A-loaded HAp/Ch-PLGA, healthy cells recover twice as fast as the malignant ones. Immunofluorescent staining of primary fibroblasts interacting with HAp/Ch-PLGA and A-HAp/Ch-PLGA particles demonstrates no negative morphological or proliferative effects on cells.
PB  - Belgrade : Materials Research Society of Serbia
C3  - Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016
T1  - Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate
SP  - 27
EP  - 27
ER  - 
@conference{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna and Vasiljević Radović, Dana and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
url = "http://dais.sanu.ac.rs/123456789/896",
abstract = "The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Previously we have shown that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous administration into mice. For this purpose radioactive 125-Iodine (125I), a low energy gamma emitter, was used to develop a novel in situ method for radiolabeling of particles and investigation of their biodistribution. In this study we utilize an emulsification process and freeze drying to load the composite particles based on hydroxyapatite nanocarrier, chitosane and poly(lactic-co-glycolic acid) with 17β- hydroxy-17α-picolyl-androst-5-en-3β-acetate (A), a chemotherapeutic derivative of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormonedependent cancers (adenocarcinoma, prostate cancer, cervix carcinoma, colon cancer, etc.). 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The synthesized particles of A-loaded HAp/Ch-PLGA were found to be spherical in shape with a uniform size distribution of d50=168 nm. The release of A from HAp/Ch-PLGA was sustained, with no burst release or plateauing after three weeks. The obtained results of the DET and MTT tests show that the particles of A-loaded HAp/Ch-PLGA exhibit almost three times higher cytotoxicity towards lung adenocarcinoma cells (A549) than towards healthy cells (MRC5), while at the same time allowing twice as fast recovery of healthy cells. We have also analyzed the period of recovery of healthy, as well as cancer cells, following the treatment with A-loaded HAp/Ch-PLGA. After treatment with A-loaded HAp/Ch-PLGA, healthy cells recover twice as fast as the malignant ones. Immunofluorescent staining of primary fibroblasts interacting with HAp/Ch-PLGA and A-HAp/Ch-PLGA particles demonstrates no negative morphological or proliferative effects on cells.",
publisher = "Belgrade : Materials Research Society of Serbia",
journal = "Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016",
title = "Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate",
pages = "27-27"
}

A Facile Determination Method for an Androstane-based Lung Cancer Inhibitor Loaded in Nano/Micro Particles Based on Hydroxyapatite by Means of DTA/TGA Coupled with On-line Mass Spectrometry

Ignjatović, Nenad; Kuzmanović, Maja; Penov Gaši, Katarina; Ajduković, Jovana; Kojić, Vesna; Uskoković, Dragan

(Belgrade : Materials Research Society of Serbia, 2015)

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Kuzmanović, Maja
AU  - Penov Gaši, Katarina
AU  - Ajduković, Jovana
AU  - Kojić, Vesna
AU  - Uskoković, Dragan
PY  - 2015
UR  - http://dais.sanu.ac.rs/123456789/826
AB  - In our study, we examined the possibilities for the application of Thermo-Gravimetric Analysis/Differential-Thermal Analysis (DTA/TGA) coupled on-line with mass spectrometry (MS) as a fingerprint for identification purposes in drug loading processes. Androstane derivative 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl acetate (2-OAc) with antitumor activity was loaded in nano hydroxyapatite (HAp) coated with chitosan-poly(D,L)-lactide-co-glycolide (Ch-PLGA) by emulsification and finally freeze-dried. By means of DTA/TGA-MS, it was quickly determined that the form of 2-OAc was the same before and after loading. The observed exothermic and endothermic processes due to the transformation of material with simultaneous analysis of gas products have proven to be successful in the analysis of drug loading processes in multi-component ceramic-polymer carriers. The loading efficiency of 74.7% was determined using the Differential Scanning Calorimetry (DSC) technique. A FT-IR analysis confirmed the qualitative composition of the synthesized 2-OAc-loaded HAp/Ch-PLGA. The in vitro antiproliferative activity was evaluated against human cell lines: lung adenocarcinoma (A549), as well as healthy fetal lung fibroblasts (MRC-5). The results of DET and MTT tests have revealed a high viability of healthy cells MRC-5 (82%) and the death of cancer cells A549 (46%) after a treatment with 2-OAc-loaded HAp/Ch-PLGA.
PB  - Belgrade : Materials Research Society of Serbia
C3  - Programme and The Book of Abstracts / Seventeenth Annual Conference YUCOMAT 205, Herceg Novi, August 31– September 4, 2015
T1  - A Facile Determination Method for an Androstane-based Lung Cancer Inhibitor Loaded in Nano/Micro Particles Based on Hydroxyapatite by Means of DTA/TGA Coupled with On-line Mass Spectrometry
SP  - 35
EP  - 35
ER  - 
@conference{
author = "Ignjatović, Nenad and Kuzmanović, Maja and Penov Gaši, Katarina and Ajduković, Jovana and Kojić, Vesna and Uskoković, Dragan",
year = "2015",
url = "http://dais.sanu.ac.rs/123456789/826",
abstract = "In our study, we examined the possibilities for the application of Thermo-Gravimetric Analysis/Differential-Thermal Analysis (DTA/TGA) coupled on-line with mass spectrometry (MS) as a fingerprint for identification purposes in drug loading processes. Androstane derivative 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl acetate (2-OAc) with antitumor activity was loaded in nano hydroxyapatite (HAp) coated with chitosan-poly(D,L)-lactide-co-glycolide (Ch-PLGA) by emulsification and finally freeze-dried. By means of DTA/TGA-MS, it was quickly determined that the form of 2-OAc was the same before and after loading. The observed exothermic and endothermic processes due to the transformation of material with simultaneous analysis of gas products have proven to be successful in the analysis of drug loading processes in multi-component ceramic-polymer carriers. The loading efficiency of 74.7% was determined using the Differential Scanning Calorimetry (DSC) technique. A FT-IR analysis confirmed the qualitative composition of the synthesized 2-OAc-loaded HAp/Ch-PLGA. The in vitro antiproliferative activity was evaluated against human cell lines: lung adenocarcinoma (A549), as well as healthy fetal lung fibroblasts (MRC-5). The results of DET and MTT tests have revealed a high viability of healthy cells MRC-5 (82%) and the death of cancer cells A549 (46%) after a treatment with 2-OAc-loaded HAp/Ch-PLGA.",
publisher = "Belgrade : Materials Research Society of Serbia",
journal = "Programme and The Book of Abstracts / Seventeenth Annual Conference YUCOMAT 205, Herceg Novi, August 31– September 4, 2015",
title = "A Facile Determination Method for an Androstane-based Lung Cancer Inhibitor Loaded in Nano/Micro Particles Based on Hydroxyapatite by Means of DTA/TGA Coupled with On-line Mass Spectrometry",
pages = "35-35"
}