In-Vitro Degradation and Cytotoxicity of Gelatin/Chitosan Microspheres for Drug Controlled Release

Abstract

The composite microspheres based on gelatin (Gel) and chitosan (Cs) loaded with 5-fluorouracil (5-FU) were fabricated using glutaraldehyde (GA) as a crosslinker. The in-vitro degradation behaviors of the Gel/Cs microspheres, including the changes of pH value, mass loss and microsphere morphology, were studied. The in-vitro cytotoxicites of Gel/Cs microspheres loaded and unloaded with 5-FU were carried out with MCF-7 breast cancer cell line. The empty Gel/Cs microspheres showed a smooth surface and were evenly distributed; however, there was much aggregation observed for the microspheres loaded with 5-FU. The degradation results showed that the pH values of both PBS and PBS-lysozyme solutions increased with increasing degradation time but the increase of pH value of PBS-lysozyme solution was quicker than that of PBS solution. The aggregated Gel/Cs microspheres lose their shape and many fibers were found after 21 days in PBS solution; while the Gel/Cs microsphere disappeared in PBS-lysozyme solution. The mass loss of the Gel/Cs microspheres in PBS-lysozyme solution was larger than that of the Gel/Cs in PBS solution. The results indicated that lysozyme can accelerate the degradation of Gel/Cs microspheres. The cytotoxicity results showed that the cell viability decreased with increasing glutaraldehyde content for the empty Gel/Cs microspheres; however, the cell viability increased with increasing glutaraldehyde content for the Gel/Cs microspheres loaded with 5-FU. Therefore, the Gel/Cs microspheres can be offered as drug carrier candidates for long-term applications of anti-cancer drugs.