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

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2016
893.pdf (57.60Kb)
Authors
Ignjatović, Nenad
Penov Gaši, Katarina
Wu, Victoria
Ajduković, Jovana
Kojić, Vesna
Vasiljević Radović, Dana
Uskoković, Vuk
Uskoković, Dragan
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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 (adenoc...arcinoma, 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.

Keywords:
hydroxyapatite / chitosan / androstane / PLGA / nanocarriers
Source:
Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016, 2016, 27-27
Publisher:
  • Belgrade : Materials Research Society of Serbia
Projects:
  • Molecular designing of nanoparticles with controlled morphological and physicochemical characteristics and functional materials based on them (RS-45004)

ISBN: 978-86-919111-1-9

[ Google Scholar ]
URI
http://dais.sanu.ac.rs/123456789/896
Collections
  • ITN SANU - Opšta kolekcija / ITS SASA - General collection
Institution
Институт техничких наука САНУ / Institute of Technical Sciences of SASA
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"
}
Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić V, Vasiljević Radović D, Uskoković V, Uskoković D. Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate. Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016. 2016;:27-27
Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V., Vasiljević Radović, D., Uskoković, V.,& Uskoković, D. (2016). Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate.
Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016Belgrade : Materials Research Society of Serbia., null, 27-27. 
Ignjatović Nenad, Penov Gaši Katarina, Wu Victoria, Ajduković Jovana, Kojić Vesna, Vasiljević Radović Dana, Uskoković Vuk, Uskoković Dragan, "Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate" null (2016):27-27

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