Potentiality of chitosan hybridized magnesium doped-hydroxyapatite (CH/Mg·HAP) for enhanced carrying of oxaliplatin: loading, release, kinetics, and cytotoxicity

Abstract

Magnesium-enriched hydroxyapatite was synthesized and integrated with chitosan, forming a bio-compatible biocomposite (CH/Mg·HAP) to be applied as a carrier of oxaliplatin (OXN) with enhanced loading, release, and therapeutic activities. The developed CH/Mg·HAP displayed better loading (234.8 mg g⁻¹) behavior as compared to the single phase of Mg·HAP (148.9 mg g⁻¹). Based on steric analysis and advanced equilibrium modeling, the integration of chitosan enhanced the existence of loading sites up to 88.3 mg g⁻¹ as compared to the existing loading receptors throughout Mg·HAP (69.4 mg g⁻¹). This validates the impact of the integrated chemical groups and enhanced surface area. Additionally, the hybridizing reactions considerably affected the loading capacity of each receptor (n = 2.66 for CH/Mg·HAP and 2.15 for Mg·HAP). This also determined the orientation of the loaded OXN ions in a vertically oriented configuration that involves various types of multi-molecular processes. The energetic parameters, including loading energy (<40 KJ mol⁻¹), suggested the dominant mechanistic impact of the physical processes (hydrogen binding and van der Waals forces). The composite also displays conterminous and regulated release patterns that extend for about 160 h at pH 5.5 and 200 h at pH 7.4. The kinetic modeling of the release activities, in addition to the obtained diffusion exponent (>0.45), indicated that erosion and diffusion reactions interact to control the releasing pathways. The unloaded CH/Mg·HAP exhibits considerable cytotoxicity against HCT-116 cancerous cells (17.8% cell viability) and its OXN-loaded sample exhibits significantly enhanced cytotoxicity (0.87% cell viability).