Improvement of anti-cancer drug efficacy via thermosensitive hydrogel in peritoneal carcinomatosis in gastric cancer

Abstract

Peritoneal carcinomatosis (PC) of gastric origin has a poor prognosis with short survival due to lack of effective therapeutic modalities. Here, we evaluated the therapeutic efficacy of an injectable thermosensitive poly (organophosphazene) (PPZ) hydrogel with docetaxel (DTX-gel) to develop an effective therapeutic agent for patient with PC. Three days after inoculation of highly metastatic 44As3Luc cells into peritoneal cavity, the mice were intravenously or intraperitoneally administered with docetaxel alone (DTX-sol IV or IP), and intraperitoneally injected with DTX-gel. The anti-tumor activity was monitored by bioluminescence live imaging system. Compared to DTX-sol IV or IP, the tumor growth was significantly reduced in the DTX-gel treated mice (p<0.0001, p=0.0001). Furthermore, the survival rate was significantly increased in the DTX-gel treated mice compared to DTX-sol IV or IP treated mice (p<0.0001, p=0.0068). Our results demonstrated that DTX-gel suppresses peritoneal metastasis by continuing release of chemotherapy agent, which leads to increase the survival rate in a PC model. Therefore, biodegradable thermosensitive hydrogel with docetaxel system can be a good anti-cancer agent for PC.