Increased systemic efficacy of aphidicolin encapsulated in liposomes.

Abstract

Aphidicolin, a tetracyclic diterpene antibiotic produced by Cephalosporium aphidicola, is under investigation as anti-cancer drug. Because of its poor solubility in water, it cannot be administered directly in vivo. Systemic application of aphidicolin glycinate or aphidicolin gamma-cyclodextrin complexes resulted in tumour growth inhibition but not in cures. To improve the pharmacokinetics, a liposomal preparation of aphidicolin was developed and tested in neuroblastoma-bearing (UKF-NB-3) mice. The loading capacity of these liposomes was limited. Therefore, 4.5 mg aphidicolin/kg body weight was the maximum aphidicolin dose that could be applied as liposomal preparation in this approach. Comparison of effects on tumour growth exhibited by aphidicolin liposomes (4.5 mg aphidicolin/kg) given for 15 consecutive days to those of gamma-cyclodextrin inclusion complexes (15 mg aphidicolin/kg) revealed comparable tumour growth inhibition, although aphidicolin concentrations were approximately 3-fold lower. This shows that liposomal encapsulation is a promising strategy for the improvement of systemic anti-cancer activity of aphidicolin.

• Authors: Martin Michaelis, Andreas Zimmer, Nganou Handjou, Jaroslav Cinatl, Jindrich Cinatl Jr
• Journal: Oncology reports (Oncol Rep) Vol. 13 Issue 1 Pg. 157-60 (Jan 2005) ISSN: 1021-335X [Print] Greece
• PMID: 15583818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• Liposomes
• Aphidicolin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, chemistry, therapeutic use)
• Aphidicolin (administration & dosage, chemistry, therapeutic use)
• Drug Carriers
• Female
• Humans
• Liposomes
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neuroblastoma (drug therapy)
• Tumor Cells, Cultured