title: 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.affiliation: Institut für Medizinische Virologie, Zentrum der Hygiene, Klinikum der J.W. Goethe-Universität, 40, 60596 Frankfurt am Main, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Nganou
authors.initials: N
authors.lastname: Handjou
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cinatl
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D016590:Aphidicolin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D016590:Aphidicolin