title: Intraperitoneal administration of cisplatin via an in situ cross-linkable hyaluronic acid-based hydrogel for peritoneal dissemination of gastric cancer.
abstract: OBJECTIVE
  To develop a drug-delivery system for the prolonged retention of intraperitoneally (i.p.) administered cisplatin (CDDP) to deliver intraperitoneal chemotherapy against peritoneal carcinomatosis effectively.
  
  
  METHODS
  CDDP was encapsulated inside an in situ cross-linkable hyaluronic acid (HA)-based hydrogel. The gelation and degradation kinetics of the hydrogel and the release kinetics of CDDP were investigated in vitro, and the antitumor effect was investigated in a mouse model of peritoneal dissemination of human gastric cancer.
  
  
  RESULTS
  The gelation time varied according to the concentration of two polymers: HA-adipic dihydrazide and HA-aldehyde. CDDP was released from the hydrogel for more than 4 days. A cell proliferation assay showed that the polymers themselves were not cytotoxic toward MKN45P, a human gastric cancer cell line. By mixing the two polymers in the peritoneum, in situ gelation was achieved. The weight of peritoneal nodules decreased in the hydrogel-conjugated CDDP group, whereas no significant antitumor effect was observed in the free CDDP group.
  
  
  CONCLUSIONS
  In situ cross-linkable HA hydrogels represent a promising biomaterial to prolong the retention and sustain the release of intraperitoneally administered CDDP in the peritoneal cavity and to enhance its antitumor effects against peritoneal dissemination.
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan, semoto-tky@umin.ac.jp.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Emoto
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Kamei
authors.forename: Hironori
authors.initials: H
authors.lastname: Ishigami
authors.forename: Takashi
authors.initials: T
authors.lastname: Suhara
authors.forename: Yukimitsu
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Taichi
authors.initials: T
authors.lastname: Ito
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003432:Cross-Linking Reagents; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007263:Infusions, Parenteral; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D010529:Peritoneal Cavity; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D002945:Cisplatin