Surgery Today

, Volume 44, Issue 5, pp 919–926

Intraperitoneal administration of cisplatin via an in situ cross-linkable hyaluronic acid-based hydrogel for peritoneal dissemination of gastric cancer

  • Shigenobu Emoto
  • Hironori Yamaguchi
  • Takao Kamei
  • Hironori Ishigami
  • Takashi Suhara
  • Yukimitsu Suzuki
  • Taichi Ito
  • Joji Kitayama
  • Toshiaki Watanabe
Original Article

Abstract

Purpose

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.

Keywords

Intraperitoneal chemotherapy Hyaluronic acid Hydrogel Cisplatin Peritoneal dissemination 

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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Shigenobu Emoto
    • 1
  • Hironori Yamaguchi
    • 1
  • Takao Kamei
    • 1
  • Hironori Ishigami
    • 1
  • Takashi Suhara
    • 2
  • Yukimitsu Suzuki
    • 2
  • Taichi Ito
    • 2
    • 3
  • Joji Kitayama
    • 1
  • Toshiaki Watanabe
    • 1
  1. 1.Department of Surgical OncologyThe University of TokyoTokyoJapan
  2. 2.Department of Chemical System EngineeringThe University of TokyoTokyoJapan
  3. 3.Center for Disease Biology and Integrative MedicineThe University of TokyoTokyoJapan

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