pH-sensitive carboxymethyl chitosan hydrogels via acid-labile ortho ester linkage for potential biomedical applications

Hydrogel systems with favorable biocompatibility and biodegradability are of much interest for application in biomaterials and tissue engineering. In this study, a new ortho ester-based acid-labile crosslink agent with dual-epoxy end groups was synthesized and crosslinked with carboxymethyl chitosan (CMCS) at different molar ratios to prepare a series of pH-sensitive hydrogels for drug delivering. Doxorubicin (DOX) was then readily loaded into the hydrogels and the in vitro release profiles indicated that the release rate increased rapidly while pH decreased from 7.4 to 5.0, which is consistent with the degradation rate of these hydrogels at corresponding pH conditions. In addition, results from MTT assay and flow cytometry demonstrated that these CMCS-based hydrogels and their degradation products have no cytotoxicity against SH-SY5Y and 293T cells. Therefore, the prepared acid-labile hydrogels could be applied in tumorous drug delivery systems and peritumoral implantation therapy by further optimization.