Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer

Eun Jung Cho, Bo Sun, Kyung Oh Doh, Erin M. Wilson, Sandra Torregrosa-Allen, Bennett D. Elzey, Yoon Yeo

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.

Original languageEnglish (US)
Pages (from-to)312-319
Number of pages8
JournalBiomaterials
Volume37
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Drug delivery
  • Empty carriers
  • Hyaluronic acid
  • Intraperitoneal chemotherapy
  • Ovarian cancer
  • Platinum

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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