title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: shutaro@kuhp.kyoto-u.ac.jp.
authors.forename: Shutaro
authors.initials: S
authors.lastname: Gunji
authors.forename: Kazukata
authors.initials: K
authors.lastname: Obama
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsui
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Sakai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D016503:Drug Delivery Systems; D005780:Gelatin; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005780:Gelatin; D002945:Cisplatin