Modified chitosan thermosensitive hydrogel enables sustained and efficient anti-tumor therapy via intratumoral injection

Thermosensitive in situ hydrogels are potential candidates to achieve intratumoral administration, nevertheless their weak mechanical strength always lead to serious drug leakage and burst. Herein, we developed a chitosan based thermosensitive hydrogel of high mechanical strength, which was modified by glutaraldehyde (GA) and polyvinyl alcohol (PVA), for intratumoral delivery of paclitaxel (PTX). The modified hydrogel system could achieve sol-gel transition at 35.79 +/- 0.4 degrees C and exhibit a 7.03-fold greater mechanical strength compared with simple chitosan hydrogel. Moreover, the drug release of PTX loaded modified hydrogel in PBS (pH 7.4) was found to be extended to 13 days. After intratumoral administration in mice bearing H22 tumors, PTX-loaded modified hydrogels exhibited a 3.72-fold greater antitumor activity compared with Taxol (R). Overall, these modified hydrogel systems demonstrated to be a promising way to achieve efficient sustained release and enhanced anti-tumor therapy efficiency of anticancer drugs through in situ tumor injectable administration. (C) 2016 Elsevier Ltd. All rights reserved.