Injectable Thermosensitive Polypeptide-Based CDDP-Complexed Hydrogel for Improving Localized Antitumor Efficacy

Abstract

In this study, a type of novel thermosensitive polypeptide-based hydrogel with tunable gelation behavior through changing the content of carboxyl groups was developed for the purpose of improving the cisplatin (CDDP) release behavior and enhancing the localized antitumor efficiency. The introduction of carboxyl groups in methoxy-poly(ethylene glycol)- b -(poly(γ-ethyl- l -glutamate- co - l -glutamic acid) (mPEG- b -P(ELG- co -LG)) not only led to adjustable mechanical properties of the hydrogel but also significantly reduced the burst release of the drug through the complexation between the carboxyl groups of polypeptide and CDDP. Furthermore, both the good biocompatibility and the biodegradable properties of mPEG- b -P(ELG- co -LG) hydrogel were observed in vivo. Interestingly, the CDDP-complexed mPEG- b -P(ELG- co -LG) hydrogel exhibited significantly enhanced antitumor efficacy in vivo compared to the mPEG- b -PELG hydrogel loaded with CDDP without complexation, although a lower cytotoxicity and IC 50 of the CDDP-complexed hydrogel was observed in vitro. Overall, the new type of injectable CDDP-complexed hydrogel may serve as an efficient platform for sustained CDDP delivery in localized tumor therapy.