Effects of Chitosan on Loading and Releasing for Doxorubicin Loaded Porous Hydroxyapatite-Gelatin Composite Microspheres

Polymers (Basel). 2022 Oct 12;14(20):4276. doi: 10.3390/polym14204276.

Abstract

Porous hydroxyapatite-gelatin (Hap-Gel) composite microspheres derived by wet chemical methods were used as carriers of doxorubicin (DOX) coupled with chitosan (Chi) for treating cancers. Through X-ray diffraction, specific surface area porosimetry, chemisorption analysis and inductively coupled plasma mass spectrometry, the crystalline phase, composition, morphology, and pore distribution of HAp-Gel microspheres were all characterized. HAp nanosized crystals and Gel polymers form porous microspheres after blending and exhibit a specific surface area of 158.64 m2/g, pore sizes from 3 to 150 nm, and pore volumes of 0.4915 cm3/g. These characteristics are suitable for carriers of DOX. Furthermore, by the addition of chitosan during drug loading, its drug-entrapment efficiency increases from 70% to 99% and the release duration increases from a 100% burst within a day to only 45% over half a year since the pores in the composite microspheres provide a shielding effect throughout the degradation period of the chitosan. According to the MTT tests, cell viability of DOX-Chi/HAp-Gel is 57.64% on day 5, similar to the result treated with DOX only. It is concluded that under the protection of pores in the microspheres, the chitosan abundant of hydroxyls combining HAp-Gel and DOX by forming hydrogen bonds indeed enhances the entrapment efficiency, prolongs the releasing period and maintains DOX's ability to perform medicine functions unaffected after loading.

Keywords: chitosan; doxorubicin; drug loading and releasing; porous hydroxyapatite/gelatin microspheres; shielding effect.