A novel drug delivery system of intraperitoneal chemotherapy for peritoneal carcinomatosis using gelatin microspheres incorporating cisplatin.

Abstract

[Background]Peritoneal carcinomatosis is a poor prognostic factor for patients with gastrointestinal, gynecologic, and pancreatic cancer. Cisplatin (CDDP) is among the most effective anti-cancer agents, although its adverse effects remain unresolved. For the treatment of peritoneal carcinomatosis with high-dose CDDP, it is necessary to design a new delivery system of CDDP that can decrease systemic toxicity and achieve a better targeted, high-dose chemotherapy. [Methods]Microspheres were prepared from gelatin of a nontoxic, biodegradable material for the sustained release of CDDP. The gelatin microspheres incorporating CDDP (GM-CDDP) were injected intraperitoneally into a mouse model of peritoneal carcinomatosis; their therapeutic efficacy and adverse effects were evaluated in comparison with intraperitoneal administration of free CDDP. [Results]GM-CDDP released CDDP in the peritoneal cavity as a result of gelatin biodegradation. Mice treated with microspheres in the peritoneal cavity lived longer than mice treated with free CDDP (74 ± 23 vs 40 ± 23 days;P < .05). The mice treated with GM-CDDP also lost no weight, whereas the free CDDP group lost approximately 20% body weight (106 ± 5% vs 80 ± 7%; P < .001; body weight on day 1 = 100%). GM-CDDP significantly decreased the nephrotoxicity and hematotoxicity of CDDP. [Conclusion]GM decreased the adverse effects of CDDP and allowed high-dose intraperitoneal chemotherapy with the control of CDDP. This technique of gradual local release may allow us to provide a high-dose, targeted, intraperitoneal chemotherapy with CDDP, resulting in enhanced anti-cancer effects. These gelatin microspheres may be useful as a drug carrier for the treatment of peritoneal carcinomatosis.