The effect of the androstane lung cancer inhibitor content on the cell-selective toxicity of hydroxyapatite-chitosan-PLGA nanocomposites
Penov Gaši, Katarina
Article (Accepted Version)
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An androstane (17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (derivative A)) cancer inhibitor was successfully captured in a carrier made of nano-sized hydroxyapatite (HAp) coated with chitosan-PLGA polymer blends (Ch-PLGA). In our previous studies, we demonstrated that it was convenient to use spherical HAp/Ch-PLGA carriers as vehicles to target the lungs following intravenous administration. In this study, we used emulsification and subsequent freeze-drying to load the spherical HAp/Ch-PLGA carriers with varying contents of the derivative A, in order to examine the selective toxicity towards cancerous/healthy lung cells. The XRD and FT-IR techniques confirmed the drug loading process, and the content of the poorly water soluble derivative A was estimated directly via the DSC technique. The particles were spherical in shape with the d50 distribution varying between 167 and 231 nm, whereas the content of the derivative A ranged from 6.5 to 19.3 wt%. Cell-selective cytotoxicity was... examined simultaneously on two cell lines: human lung carcinoma (A549 ATCC CCL 185) and human lung fibroblasts (MRC-5 ATCC CCL 171). All particles exhibited nearly three times larger cytotoxicity towards cancer cells (A549) than towards healthy cells (MRC5), where the particles with the derivative A content of 6.5 wt% allowed for the viability of healthy cells >80%. Ninety-six hours after the treatment of cells with particles with different contents of derivative A (after incubation and recovery), recovery was faster in damaged healthy cells than in cancerous cells.
Keywords:androstane / hydroxyapatite / nanocarriers / drug delivery / cancer cell targeting / cell-selective cytotoxicity
Source:Materials Science and Engineering: C, 2018, 89, 1, 371-377
- Molecular designing of nanoparticles with controlled morphological and physicochemical characteristics and functional materials based on them (RS-45004)
- This is the peer-reviewed version of the article: Ignjatović, N.L., K.M. Penov-Gaši, J.J. Ajduković, V.V. Kojić, S.B. Marković, and D.P. Uskoković. 2018. “The Effect of the Androstane Lung Cancer Inhibitor Content on the Cell-Selective Toxicity of Hydroxyapatite-Chitosan-PLGA Nanocomposites.” Materials Science and Engineering C 89: 371–77. https://doi.org/10.1016/j.msec.2018.04.028.