FF-10832 enables long survival via effective gemcitabine accumulation in a lethal murine peritoneal dissemination model

Cancer Sci. 2019 Sep;110(9):2933-2940. doi: 10.1111/cas.14123. Epub 2019 Aug 1.

Abstract

Chemotherapy has been the treatment of choice for unresectable peritoneal dissemination; however, it is difficult to eradicate such tumors because of poor drug delivery. To solve this issue, we developed FF-10832 as liposome-encapsulated gemcitabine to maintain a high concentration of gemcitabine in peritoneal tumors from the circulation and ascites. A syngeneic mouse model of peritoneal dissemination using murine Colon26 cell line was selected to compare the drug efficacy and pharmacokinetics of FF-10832 with those of gemcitabine. Despite the single intravenous administration, FF-10832 treatment enabled long-term survival of the lethal model mice as compared with those treated with gemcitabine. Pharmacokinetic analysis clarified that FF-10832 could achieve a more effective gemcitabine delivery to peritoneal tumors owing to better stability in the circulation and ascites. The novel liposome-encapsulated gemcitabine FF-10832 may be a curative therapeutic tool for cancer patients with unresectable peritoneal dissemination via the effective delivery of gemcitabine to target tumors.

Keywords: gemcitabine; liposomes; nanotechnology; peritoneal neoplasms; survival analysis.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Ascites / etiology
  • Ascites / metabolism*
  • Cell Line, Tumor / transplantation
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Stability
  • Female
  • Humans
  • Injections, Intravenous
  • Kaplan-Meier Estimate
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Peritoneal Neoplasms / complications
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / pathology
  • Peritoneum / pathology*
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Liposomes
  • Deoxycytidine
  • gemcitabine