Lipid-complexed camptothecin: Formulation and initial biodistribution and antitumor activity studies

Steven M. Sugarman, Yiyu Zou, Kishor Wasan, Ken Poirot, Robert Kumi, Sara Reddy, Roman Perez-Soler

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Water-soluble derivatives of camptothecin, an active topoisomerase I inhibitor, have shown a broad spectrum of activity against human tumors. Early clinical trials with the water-soluble sodium salt of camptothecin were hindered by significant cystitis, gastroenteritis, and leukopenia. Furthermore, the sodium salt of camptothecin has been shown to have significantly less activity than the water-insoluble lactone form of the compound. We describe a formulation of lipid-complexed CPT (LC-CPT; particle size range 20.8-208.1 nm) that is very easy to prepare and allows for intravenous administration in vivo in clinically relevant lipid-drug ratios (12.5:1 w/w). The lipid formulation had in vitro antitumor activity similar to that of CPT formulated without lipids and displayed similar cytotoxicity against MDR-1-negative and -positive tumor cells. The biodistribution of CPT was profoundly affected by lipid complexation; free CPT achieved the greatest concentration in the pulmonary parenchyma while LC-CPT achieved the highest concentration in the gastrointestinal tract. LC-CPT had significant antitumor activity in vivo against intraperitoneal L1210 and P388 leukemia and appeared to be more potent than free CPT.

Original languageEnglish (US)
Pages (from-to)531-538
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume37
Issue number6
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Lipid-complexed camptothecin

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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