Fibrinogen-coated droplets of olive oil for delivery of docetaxel to a fibrin(ogen)-rich ascites form of a murine mammary tumor

Charity M. Einhaus, Andrew C. Retzinger, Andre O. Perrotta, Michael D. Dentler, Abhijeet S. Jakate, Pankaj B. Desai, Gregory S. Retzinger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Micronized droplets of olive oil loaded with docetaxel and coated with functional fibrinogen were administered intraperitoneally to mice bearing the fibrin(ogen)-rich ascites form of the TA3/St mammary tumor. When compared with docetaxel administered intraperitoneally as its commercial formulation (i.e., Taxotere), docetaxel-loaded oil droplets coated with murine fibrinogen prolonged the median survival time of tumor-bearing mice from 14.5 to 29.5 days. Drug-free oil droplets provided no therapeutic benefit. Significantly more docetaxel was associated with tumor cells 24 and 48 hours after administration of the drug in fibrinogen-coated oil droplets than after its administration as Taxotere. Consistent with a role for thrombin in the retention of fibrinogen-coated oil droplets within the tumor microenvironment, hirudin significantly reduced the association of tumor cells with docetexel delivered in fibrinogen-coated oil droplets and, at the same time, reduced the therapeutic efficacy of the droplets to that of Taxotere. Importantly, fibrinogen-coated oil droplets formed rosettes with tumor cells in vivo, a process prevented by hirudin. Although mice treated with oil droplets developed antifibrinogen antibodies, those antibodies seemed to be inconsequential. Taken together, our results and observations indicate fibrinogen-coated oil droplets markedly improve the therapeutic efficacy of docetaxel for the treatment of a mammary tumor grown in ascites form, a consequence of thrombin-mediated retention of the drug-loaded droplets within the tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)7001-7010
Number of pages10
JournalClinical Cancer Research
Volume10
Issue number20
DOIs
StatePublished - Oct 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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