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Sakač, Marija

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  • Sakač, Marija (4)
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Author's Bibliography

Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor

Ignjatović, Nenad; Sakač, Marija; Kuzminac, Ivana; Kojić, Vesna V.; Marković, Smilja; Wu, Victoria; Uskoković, Vuk; Uskoković, Dragan

(Belgrade : Materials Research Society of Serbia, 2018)

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna V.
AU  - Marković, Smilja
AU  - Wu, Victoria
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2018
UR  - http://dais.sanu.ac.rs/123456789/3662
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. Hybrid systems based on nano hydroxyapatites (HAp) are the subject of numerous studies in preventive and regenerative medicine. HAp nanoparticles coated with bioresorbable polymers have been successfully used as fillers, carriers of antibiotics, vitamins and stem cells in bone tissue engineering, etc. In this study we utilize an emulsification process and freeze drying to load the hybrid system made of nano HAp particles coated with chitosan oligosaccharide lactate (ChOSL) with two different but similar steroid derivatives: 3β-hydroxy- 16-hydroxymino-androst-5-ene-17-one (A), C19H27NO3 and 3β, 17β-dihydroxy-16-hydroxyminoandrost- 5-ene (B), C19H29NO3. The cell-selective toxicity of HAp particles coated with of A- or B-loaded ChOSL was examined simultaneously on the following cell lines: human breast carcinoma (MCF-7, MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5), using dye exclusion (DET) and MTT assays. 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivatives A or B. FT-IR, XRD, DTA, TGA and DSC techniques confirmed the drug loading process of steroide (A or B) in core–shell particles based on nano hydroxyapatite. Atomic force microscopy and particle size analyses were used to confirm that the particles were spherical with sizes between 80 and 240 nm. The measured values of electrokinetic parameters (zeta potential, electrophoretic mobility and conductivity) were significantly different for the steroid free carrier (HAp/ChOLS) and A- or B-loaded ChOSL. The value of the topological molecular polar surface area (TPSA, the sum of the surfaces of polar atoms and groups in the molecule), were also different for drug free carrier and A- or BHAp/ ChOLS. Highly selective anticancer activity was noted towards breast cancer cells (MDAMB- 231) by B-loaded HAp/ChOLS. DET testing after 48 hours (after incubation and recovery) of the treatment with A-HAp/ChOSL and B-HAp/ChOSL particles showed a high viability of healthy cells (over 80%). The lowest viability was found in MDA-MB-231 cancer cells treated with B-HAp/ChOSL (28%). The obtained results of the DET and MTT tests showed that the particles of A-HAp/ChOLS exhibited nearly four-fold greater cytotoxicity towards breast cancer cells (MDA-MB-231) than towards healthy cells (MRC-5). B-HAp/ChOSL particles exhibited nearly six times greater cytotoxicity to all breast cancer cells than to healthy ones.
PB  - Belgrade : Materials Research Society of Serbia
C3  - Programme and The Book of Abstracts / Twentieth Annual Conference YUCOMAT 2018, Herceg Novi, September 3-7, 2018
T1  - Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor
SP  - 74
EP  - 75
ER  - 
@conference{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna V. and Marković, Smilja and Wu, Victoria and Uskoković, Vuk and Uskoković, Dragan",
year = "2018",
url = "http://dais.sanu.ac.rs/123456789/3662",
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. Hybrid systems based on nano hydroxyapatites (HAp) are the subject of numerous studies in preventive and regenerative medicine. HAp nanoparticles coated with bioresorbable polymers have been successfully used as fillers, carriers of antibiotics, vitamins and stem cells in bone tissue engineering, etc. In this study we utilize an emulsification process and freeze drying to load the hybrid system made of nano HAp particles coated with chitosan oligosaccharide lactate (ChOSL) with two different but similar steroid derivatives: 3β-hydroxy- 16-hydroxymino-androst-5-ene-17-one (A), C19H27NO3 and 3β, 17β-dihydroxy-16-hydroxyminoandrost- 5-ene (B), C19H29NO3. The cell-selective toxicity of HAp particles coated with of A- or B-loaded ChOSL was examined simultaneously on the following cell lines: human breast carcinoma (MCF-7, MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5), using dye exclusion (DET) and MTT assays. 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivatives A or B. FT-IR, XRD, DTA, TGA and DSC techniques confirmed the drug loading process of steroide (A or B) in core–shell particles based on nano hydroxyapatite. Atomic force microscopy and particle size analyses were used to confirm that the particles were spherical with sizes between 80 and 240 nm. The measured values of electrokinetic parameters (zeta potential, electrophoretic mobility and conductivity) were significantly different for the steroid free carrier (HAp/ChOLS) and A- or B-loaded ChOSL. The value of the topological molecular polar surface area (TPSA, the sum of the surfaces of polar atoms and groups in the molecule), were also different for drug free carrier and A- or BHAp/ ChOLS. Highly selective anticancer activity was noted towards breast cancer cells (MDAMB- 231) by B-loaded HAp/ChOLS. DET testing after 48 hours (after incubation and recovery) of the treatment with A-HAp/ChOSL and B-HAp/ChOSL particles showed a high viability of healthy cells (over 80%). The lowest viability was found in MDA-MB-231 cancer cells treated with B-HAp/ChOSL (28%). The obtained results of the DET and MTT tests showed that the particles of A-HAp/ChOLS exhibited nearly four-fold greater cytotoxicity towards breast cancer cells (MDA-MB-231) than towards healthy cells (MRC-5). B-HAp/ChOSL particles exhibited nearly six times greater cytotoxicity to all breast cancer cells than to healthy ones.",
publisher = "Belgrade : Materials Research Society of Serbia",
journal = "Programme and The Book of Abstracts / Twentieth Annual Conference YUCOMAT 2018, Herceg Novi, September 3-7, 2018",
title = "Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor",
pages = "74-75"
}

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

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"
}