The antitumor effect of a thermosensitive polymeric hydrogel containing paclitaxel in a peritoneal carcinomatosis model
- 29 July 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 30 (1), 1-7
- https://doi.org/10.1007/s10637-010-9499-y
Abstract
The prognosis of peritoneal carcinomatosis is regarded as poor because safe, effective therapeutic modalities are lacking. Intraperitoneal chemotherapy is one treatment option, involving the delivery of a high concentration of chemotherapeutic drugs into the abdominal cavity, but the severe side effects associated with such treatment are a major obstacle in clinical application. We evaluated the anti-cancer effects of intraperitoneal delivery of a thermosensitive polymeric hydrogel containing chemotherapeutics in an animal model of carcinomatosis. The progress of peritoneal carcinomatosis, introduced by injecting a luciferase-transfected human gastric cancer cell line (HSC44Luc) into the peritoneal cavity of nude mice, was quantitatively evaluated by in vivo bioluminescence imaging. Three days after intraperitoneal (IP) injection of HSC44Luc cells, treatment solutions were injected into the peritoneal cavity. Mice were categorized into four groups depending on treatment method; these were (1) a control PBS group (n = 5), (2) a hydrogel-only group (n = 5), (3) a paclitaxel solution (30 mg/kg) group (n = 3), and (4) a hydrogel-with-paclitaxel (15 mg/kg) group (n = 5). Quantitative photon counting was performed weekly in each animal. Mice were sacrificed on the 5th or 28th day after treatment, for pathologic evaluation. In vivo bioluminescence imaging showed that photon counts in the hydrogel-with-paclitaxel and paclitaxel solution groups were significantly lower than in the PBS group over the entire experimental period. Although neither group of responding mice showed any peritoneal nodules on the 28th day after treatment, only the paclitaxel solution group exhibited dilated edematous changes in the intestine; these side effects were absent in animals treated with hydrogel-with-paclitaxel group. In conclusion, a thermosensitive hydrogel containing paclitaxel may be a safe and effective treatment option for peritoneal carcinomatosis.Keywords
This publication has 23 references indexed in Scilit:
- Intelligent Drug Delivery SystemsBioconjugate Chemistry, 2009
- Should the Treatment of Peritoneal Carcinomatosis by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Still be Regarded as a Highly Morbid Procedure?Annals of Surgery, 2009
- Thermosensitive poly(organophosphazene)–paclitaxel conjugate gels for antitumor applicationsBiomaterials, 2009
- Suppression of in vivo tumor growth by using a biodegradable thermosensitive hydrogel polymer containing chemotherapeutic agentInvestigational New Drugs, 2009
- Treatment of peritoneal dissemination from gastric cancer by peritonectomy and chemohyperthermic peritoneal perfusionBritish Journal of Surgery, 2005
- Advancing the field of drug delivery: Taking aim at cancerCancer Cell, 2003
- Advancing animal models of neoplasia through in vivo bioluminescence imagingEuropean Journal of Cancer, 2002
- A Thermosensitive Poly(organophosphazene) GelMacromolecules, 2002
- PaclitaxelDrugs, 1994
- Positive Results of Combined Therapy of Surgery and Intraperitoneal Hyperthermic Perfusion for Far-advanced Gastric CancerAnnals of Surgery, 1990