Dynamic imine bond cross-linked self-healing thermosensitive hydrogels for sustained anticancer therapy via intratumoral injection

Highlights: • A self-healing thermosensitive hydrogel based on the dynamic chemistry bond was developed. • Dox was encapsulated into these hydrogels for antitumor therapy via in situ injection. • These gels exhibited sol-gel transition at 37 °C within 5 min and satisfactory self-healing ability. • The in vitro release of DOX-loaded modified gels in pH 7.4 PBS was extended for 13 d. • The drug loaded gels showed a superior tumor inhibition efficiency with good biocompatibility. - Abstract: In this study, we developed a self-healing thermosensitive gel, via dialdehyde-functionalized polyethylene glycol (DF-PEG) and β-glycerophosphate (GP) cross-linked chitosan (CS) hydrogels, which enable autonomous self-healing upon damage and sustained release of doxorubicin hydrochloride (DOX) for antitumor therapy via intratumoral injection. The cross-linked gels could exhibit sol-gel transition at 37 °C within 5 min and satisfactory in vitro and in vivo healing ability by observing the rejoining and fusion process of scratched gels. Moreover, the in vitro release of DOX loaded cross-linked gels in PBS (pH 6.5 and 7.4) was found to be extended to 13 d. After intratumoral injection in Heps tumor-bearing mice, the drug loaded self-healing thermosensitive gels showed a superior tumor inhibition rate (66.12%) than CS thermosensitive hydrogels (53.23%), while the histology studies gave the relieved cardiotoxicity and good biocompatibility of the cross-linked gels. Overall, these cross-linked gels could become a potential local drug delivery system to achieve efficient sustained release, relieved side effects and enhanced therapy efficiency through localized administration.