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01-09-2006 | Original Article

Liposome formulation of a novel hydrophobic aryl-imidazole compound for anti-cancer therapy

Authors: Jubo Liu, Helen Lee, Mario Huesca, Aiping Young, Christine Allen

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2006

Abstract

Purpose: A cholesterol-free liposome formulation formed from mixtures of egg phosphatidylcholine (ePC) and poly (ethylene glycol) conjugated distearoylphosphatidylethanolamine (DSPE-PEG 2000) was optimized and evaluated for delivery of a novel anti-cancer agent ML220 (2-(5-bromo-1H-indol-3-yl)-1H-phenanthro [9,10-d] imidazole). Results and Discussion: ML220 is highly lipophilic with a water solubility of 0.14 μg/ml and calculated log P of 5.69. The ML220-loaded liposomes had a unimodal size-distribution and a mean diameter of 89 nm. The drug to lipid ratio in the formulation was 1:3.5 (mol:mol) and the drug loading efficiency was 83% providing a more than 50,000-fold increase in the water solubility of ML220. The formulation was demonstrated to be stable in vitro at 37°C for over 2 weeks with a delayed drug release profile. Evaluation of the subacute toxicity of the liposome formulated drug in C3H mice revealed no overt signs of toxicity. Also, a biexponential drug plasma concentration pattern was found upon evaluation of the pharmacokinetics in Balb/C mice. The in vivo evaluation of the anti-cancer activity in a human colon HT29 carcinoma model revealed a significant delay in tumor growth. Conclusion: Overall, the ePC/DSPE-PEG liposomes were demonstrated to be a suitable delivery system for ML220. These studies also highlight the potential of cholesterol-free liposomes as a formulation strategy for highly lipophilic drugs.

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Title: Liposome formulation of a novel hydrophobic aryl-imidazole compound for anti-cancer therapy
Authors: Jubo Liu
Helen Lee
Mario Huesca
Aiping Young
Christine Allen
Publication date: 01-09-2006
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2006
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-005-0161-x

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