Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
Authors
Ignjatović, Nenad
Penov Gaši, Katarina
Wu, Victoria
Ajduković, Jovana
Kojić, Vesna V.
Vasiljević-Radović, Dana

Kuzmanović, Maja
Uskoković, Vuk
Uskoković, Dragan P.

Article (Accepted Version)
Metadata
Show full item recordAbstract
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.
Keywords:
androstane / chitosan / hydroxyapatite / lung cancer / PLGASource:
Colloids and Surfaces B: Biointerfaces, 2016, 148, 629-639Projects:
- 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), Grant R00-DE021416
Note:
- This is the peer-reviewed version of the articleIgnjatović, N.L., Penov-Gaši, K.M., Wu, V.M., Ajduković, J.J., Kojić, V.V., Vasiljević-Radović, D., Kuzmanović, M., Uskoković, V., Uskoković, D.P., 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: Biointerfaces 148, 629–639. https://doi.org/10.1016/j.colsurfb.2016.09.041
DOI: 10.1016/j.colsurfb.2016.09.041
ISSN: 0927-7765 (Print); 1873-4367 (Online)
PubMed: 27694053