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.
Highlights
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death around the world [1]
Our results demonstrated that DTX-gel suppresses peritoneal metastasis by continuing release of chemotherapy agent, which leads to increase the survival rate in a peritoneal carcinomatosis (PC) model
The hydrogel was solved in phosphate buffered saline (PBS), which displayed solution-to-gel and gel-to-solution transition according to temperature change
Summary
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death around the world [1]. The systemic chemotherapy has a poor penetration of anti-cancer drugs into the peritoneal cavity due to the peritoneal-plasma barrier comprising of mesothelium and submesothelial tissues [4]. To improve the penetration efficiency in the peritoneal cavity, intraperitoneal (IP) chemotherapy for patients with PC has been conducted, because IP chemotherapy methods can expose much higher drug concentration to peritoneal tumors than systemic chemotherapy [5, 6]. De Castro et al conducted a randomized phase III trial, which demonstrated that administration of intraperitoneal anti-cancer drug in ovarian cancer patients with peritoneal dissemination had longer overall survival due to high local concentration of anti-cancer drug in peritoneal cavity [7]. Intraperitoneal administration has several limitations such as systemic and local toxicity including abdominal pain, adhesion formation, and chemical peritonitis caused by failure of control release of anticancer drugs [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
