Chitosan/calcium phosphate microspheres as smart, multi-functional delivery systems for targeted bone cancer...

The advancement of current bone cancer treatments lies in targeted drug administration using smart drug delivery systems. pH-responsive chitosan-based microcarriers are promising systems for the loading and simultaneous release of antitumor drugs and therapeutic metal ions. The incorporation of calcium phosphate (CaP) bioceramic can enhance the functionality of microcarriers by increasing the loading capacity of hydrophilic drugs through favorable interactions. In this study, we prepared chitosan-copper(II)/CaP microspheres as potential microcarriers of doxorubicin (DOX). Bulk composite microspheres with an average diameter between 50 and 110 µm, and a circularity factor of ∼1 were produced by the electrohydrodynamic atomization process, while the successful DOX loading into chitosan-Cu/CaP microspheres was confirmed by fluorescence microscopy. Drug release study was evaluated in vitro in phosphate buffer solutions (pH 6 and pH 7.4), confirming the pH-sensitivity of microspheres, while the highest quantity of released drug was detected in complete cell culture medium. Furthermore, the enhanced drug release in different buffers was achieved by the incorporation of CaP bioceramics at different quantities (5 and 10 wt%). The cytotoxicity evaluation on osteosarcoma (MG-63) and adult human dermal fibroblasts (HDFa) cells revealed the toxicity of microspheres in a concentration-dependent manner, while DOX-loaded microspheres modified with CaP indicated cytotoxicity even at lower concentrations. This property opens the possibility to apply the developed systems locally at a lower dosage.