Selective Anticancer Activity of Hydroxyapatite/Chitosan-poly(d,l)-lactide-co-glycolide Particles Loaded with an Androstane-Based Cancer Inhibitor

Authors

Nenad Ignjatović, Serbian Academy of Sciences and ArtsFollow
Katarina M. Penov-Gaši, University of Novi Sad
Victoria M. Wu, Chapman University
Jovana J. Ajduković, University of Novi Sad
Vesna V. Kojić, University of Novi Sad
Dana Vasiljević-Radović, University of Belgrade
Maja Kuzmanović, Serbian Academy of Science and Arts
Vuk Uskoković, Chapman UniversityFollow
Dragab Uskoković, Serbian Academy of Sciences and Arts

Document Type

Article

Publication Date

9-28-2016

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.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Colloids and Surfaces B: Biointerfaces. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Colloids and Surfaces B: Biointerfaces, volume 148, in 2016. DOI: 10.1016/j.colsurfb.2016.09.041

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Recommended Citation

Ignjatović NL, Penov-Gaši KM, Wu VM, Ajduković JJ, Kojić VV, Vasiljević-Radović D, Kuzmanović M, Uskoković V, Uskoković DP. Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. Colloids Surf B Biointerfaces. 2016;148:629-639. doi: 10.1016/j.colsurfb.2016.09.041

Copyright

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.