A novel chitosan-based thermosensitive hydrogel containing doxorubicin liposomes for topical cancer therapy

Abstract

Thermosensitive hydrogel containing drug-loaded liposomes delivery system offers the possibility of reduced dosing frequency and sustained drug action. In the study, a soluble chitosan derivative, N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride, was used and interacted with glycerophosphate to produce a thermosensitive hydrogel as the matrix of doxorubicin-loaded liposomes. The formulation could retain the liquid state with good fluidity below or at room temperature for long time but turn into a nonflowing gel after exposing to body temperature for no more than 5 min. The mean size of liposomes was increased when dispersed into the hydrogel, while the entrapment efficiency of doxorubicin in liposomes was not discounted by the hydrogel, which was over 90%. The in vitro release experiment performed with a dialysis membrane model showed that the liposomes-containing hydrogel exhibited an excellent sustained-release behavior, which eliminated the initial burst release occuring in the liposomal formulation and only released about 22% loaded drug in 9 days. In vivo antitumor activity was evaluated by the survival time of H22-bearing mice treated with various doxorubicin formulation, which showed that the hydrogel enhanced the antitumor activity and reduced the systemic toxicity. Thus, all these results demonstrated that the thermosensitive hydrogel with embedded liposomes is a promising antitumor drug carrier for topical cancer therapy.

Keywords:

• thermosensitive hydrogel
• liposomes
• quaternary chitosan
• in vitro release
• antitumor

Acknowledgments

This work was partly supported by the National Natural Science Foundation of China (NSFC No. 81102396) and the Zhejiang Province Science and Technology Department Project (Grant No. 2012C33095).