Liposomal formulations of poorly soluble camptothecin: Drug retention and biodistribution

Goril Eide Flaten, Ting Tung Chang, William T. Phillips, Martin Brandl, Ande Bao, Beth Goins

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Camptothecin (CPT) represents a potent anticancer drug. However, its therapeutic use is impaired by both drug solubility, hydrolysis, and protein interactions in vivo. Use of liposomes as a drug-formulation approach could overcome some of these challenges. The aim of this study was to perform a mechanistic study of the incorporation and retention of the lipophilic parent CPT compound in different liposome formulations using radiolabeled CPT and thus to be able to identify promising CPT delivery systems. In this context, we also wanted to establish an appropriate mouse tumor model, in vivo scintigraphic imaging, and biodistribution methodology for testing the most promising formulation. CPT retention in various liposome formulations after incubation in buffer and serum was determined. The HT-29 mouse tumor model, 111In-labeled liposomes, as well as 3H-labeled CPT were used to investigate the biodistribution of liposomes and drug. The ability of different liposome formulations to retain CPT in buffer was influenced by lipid concentration and drug/lipid ratio, rather than lipid composition. The tested formulations were cleared from the blood in the following order: CPT solution > CPT liposomes > 111In-labeled liposomes, and liposomes mainly accumulated in the liver. Lipid composition did not influence CPT retention to the same extent as earlier observed from incorporation studies. The set-up for the biodistribution study works well and is suited for future in vivo studies on CPT liposomes. The biodistribution study showed that liposomes circulated longer than free drug, but premature release of drug from liposomes occurred. Further studies to develop formulations with higher retention potential and prolonged circulation are desired.

Original languageEnglish (US)
Pages (from-to)70-81
Number of pages12
JournalJournal of Liposome Research
Volume23
Issue number1
DOIs
StatePublished - Mar 1 2013

Keywords

  • Colon cancer
  • H-labeled CPT
  • HT-29 mouse tumor xenograft model
  • In-labeled liposomes
  • Scintigraphic imaging

ASJC Scopus subject areas

  • Pharmaceutical Science

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