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Pharmacology and efficacy of liposome-entrapped albendazole in experimental secondary alveolar echinococcosis and effect of co-administratration with cimetidine

Published online by Cambridge University Press:  06 April 2009

H. Wen ,
R. R. C. New ,
M. Muhmut ,
J. H. Wang ,
Y. H. Wang ,
J. H. Zhang ,
Y. M. Shao  and
P. S. Craig
H. Wen
Affiliation:
Department of Biological Sciences, University of Salford, Salford M5 4WT, UK Department of Surgery and Hydatid Research Unit, Xinjiang Medical College, Urumqi 830000, Xinjiang, P.R., China
R. R. C. New
Affiliation:
Cortecs Research Laboratory, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N TAX, UK
M. Muhmut
Affiliation:
Department of Surgery and Hydatid Research Unit, Xinjiang Medical College, Urumqi 830000, Xinjiang, P.R., China
J. H. Wang
Affiliation:
Department of Surgery and Hydatid Research Unit, Xinjiang Medical College, Urumqi 830000, Xinjiang, P.R., China
Y. H. Wang
Affiliation:
Department of Surgery and Hydatid Research Unit, Xinjiang Medical College, Urumqi 830000, Xinjiang, P.R., China
J. H. Zhang
Affiliation:
Department of Surgery and Hydatid Research Unit, Xinjiang Medical College, Urumqi 830000, Xinjiang, P.R., China
Y. M. Shao
Affiliation:
Department of Surgery and Hydatid Research Unit, Xinjiang Medical College, Urumqi 830000, Xinjiang, P.R., China
P. S. Craig*
Affiliation:
Department of Biological Sciences, University of Salford, Salford M5 4WT, UK
*
*Corresponding author. Department of Biological Sciences, University of Salford, Salford MS 4WTUK. Tel: 0161 745 5488. Fax: 0161 745 5210. E-mail: p.s [email protected].
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Summary

Encapsulation of the benzimidazole albendazole in multilamellar liposomes results in a preparation in which this normally insoluble anti-hydatid drug is well solublilized in aqueous media. The high entrapment efficiency observed (75–87%) and the stability of the formulation make this a promising delivery vehicle for improved chemotherapy with albendazole. In particular, the high degree of association with phospholipid may give rise to increased oral bioavailability. Oral adminisration of albendazole in liposomes led to increased concentration and/or altered metabolism of albendazole sulphoxide (ABZSX) in liver and/or plasma in non-infected Wistar rats. Results from experiments using cotton rats (Sigmodon hispidus) infected with metacestodes of Echinococcus multilocularis show that entrapment within liposomes clearly increases the uptake of albendazole via the oral route. This was reflected by increased levels of albendazole and the two major metabolites in plasma, liver and cyst homogenate when a dose of liposomal albendazole (35 mg/kg) was given orally compared to free albendazole at 50 mg/kg. There was a 75–94% reduction in biomass of the metacestode and a significant increase in survival time for the animals treated with liposome entrapped albendazole. A clear difference in distribution of albendazole and its metabolites in the liver and the metacestode tissues in the presence of cimetidine indicated that the latter has a profound effect on the metabolism of albendazole. There appeared to be a synergistic interaction between albendazole and cimetidine, since the metabolism of albendazole was markedly altered in the combined cimetidine/liposome–albendazole group, and higher therapeutic effect was observed. These findings indicate potential both for improvement of treatment of larval E. multilocularis infection and for reduction of albendazole dose levels.

Keywords

liposomealbendazolechemotherapycimetidineEchinococcus multilocularis
Type
Research Article
Information
Parasitology , Volume 113 , Issue 2 , August 1996 , pp. 111 - 121
Copyright
Copyright © Cambridge University Press 1996

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