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

Authorized Users Only
2016
Authors
Ignjatović, Nenad
Penov Gaši, Katarina
Wu, Victoria
Ajduković, Jovana
Kojić, Vesna V.
Vasiljević Radović, Dana
Kuzmanović, Maja
Uskoković, Vuk
Uskoković, Dragan
Article (Published version)
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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 s...ustained, 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.

Keywords:
androstane / chitosan / Hydroxyapatite / Nanoparticle / PLGA
Source:
Colloids and Surfaces B: Biointerfaces, 2016, 148, 629-639
Publisher:
  • Elsevier
Projects:
  • Molecular designing of nanoparticles with controlled morphological and physicochemical characteristics and functional materials based on them (RS-45004)
  • Synthesis, characterization and biological investigation of steroid derivatives and their molecular aggregates (RS-172021)
  • United States National Institutes of Health (NIH) / National Institute of Dental and Craniofacial Research (NIDCR), Grant K99-DE021416

DOI: 10.1016/j.colsurfb.2016.09.041

ISSN: 0927-7765

PubMed: 27694053

WoS: 000388248500073

Scopus: 2-s2.0-84989184184
[ Google Scholar ]
19
15
URI
http://dais.sanu.ac.rs/123456789/15974
Collections
  • ITN SANU - Opšta kolekcija / ITS SASA - General collection
Institution
Институт техничких наука САНУ / Institute of Technical Sciences of SASA
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"
}
Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić VV, Vasiljević Radović D, Kuzmanović M, Uskoković V, Uskoković D. Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. Colloids and Surfaces B: Biointerfaces. 2016;148:629-639
Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V. V., Vasiljević Radović, D., Kuzmanović, M., Uskoković, V.,& Uskoković, D. (2016). Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor.
Colloids and Surfaces B: BiointerfacesElsevier., 148, 629-639. 
https://doi.org/10.1016/j.colsurfb.2016.09.041
Ignjatović Nenad, Penov Gaši Katarina, Wu Victoria, Ajduković Jovana, Kojić Vesna V., Vasiljević Radović Dana, Kuzmanović Maja, Uskoković Vuk, Uskoković Dragan, "Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor" 148 (2016):629-639,
https://doi.org/10.1016/j.colsurfb.2016.09.041 .

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