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 journalArticle

36 Citations (Scopus)

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

Fingerprint

Camptothecin
Lipids
Water
Tumors
Salts
Sodium
Leukemia P388
Topoisomerase I Inhibitors
Leukemia L1210
Cystitis
Leukopenia
Gastroenteritis
Lactones
Cytotoxicity
Complexation
Particle Size
Human Activities
Intravenous Administration
Gastrointestinal Tract
Neoplasms

Keywords

  • Lipid-complexed camptothecin

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Lipid-complexed camptothecin : Formulation and initial biodistribution and antitumor activity studies. / Sugarman, Steven M.; Zou, Yiyu; Wasan, Kishor; Poirot, Ken; Kumi, Robert; Reddy, Sara; Perez-Soler, Roman.

In: Cancer Chemotherapy and Pharmacology, Vol. 37, No. 6, 1996, p. 531-538.

Research output: Contribution to journalArticle

Sugarman, Steven M. ; Zou, Yiyu ; Wasan, Kishor ; Poirot, Ken ; Kumi, Robert ; Reddy, Sara ; Perez-Soler, Roman. / Lipid-complexed camptothecin : Formulation and initial biodistribution and antitumor activity studies. In: Cancer Chemotherapy and Pharmacology. 1996 ; Vol. 37, No. 6. pp. 531-538.
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