RESUMO
Doxorubicin (DOX) is a chemotherapeutic drug used in osteosarcoma treatments, usually administrated in very high dosages. This study proposes novel DOX microcarriers based on chitosan (CHT) physically crosslinked with copper(II) ions that will act synergically to inhibit tumor growth at lower drug dosage without affecting the healthy cells. Spherical CHT-Cu microparticles with a smooth surface and an average size of 30.1 ± 9.1 µm were obtained by emulsion. The release of Cu2+ ions from the CHT-Cu microparticles showed that 99.4 % of added cupric ions were released in 72 h of incubation in a complete cell culture medium (CCM). DOX entrapment in microparticles was conducted in a phosphate buffer solution (pH 6), utilizing the pH sensitivity of the polymer. The successful drug-loading process was confirmed by DOX emitting red fluorescence from drug-loaded microcarriers (DOX@CHT-Cu). The drug release in CCM showed an initial burst release, followed by sustained release. Biological assays indicated mild toxicity of CHT-Cu microparticles on the MG-63 osteosarcoma cell line, without affecting the viability of human mesenchymal stem cells (hMSCs). The DOX@CHT-Cu microparticles at concentration of 0.5 mg mLâ1 showed selective toxicity toward MG-63 cells.
