Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-10T11:09:05.507Z Has data issue: false hasContentIssue false
  • English
  • Français

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 craig@bioSci.salford.ac.uk.
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Ammann, R. & Eckert, J. (1995). Clinical diagnosis and treatment of echinococcus in humans. In The Biology of Echinococcus and Hydatidosis, (ed. Thompson, R. C. A. & Lymbery, A. J.) pp. 411–451. Cab International Wallingford, Oxon, UK.Google Scholar
Bangham, A. D. & Horne, R. W. (1964). Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. Journal of Molecular Biology 8, 660–668.CrossRefGoogle ScholarPubMed
Bekhti, A. & Pirotte, J. (1987). Cimetidine increases serum mebendazole concentrations: Implications for treatment of hepatic hydatid cysts. British Journal of Clinical Pharmacology 24, 390–392.CrossRefGoogle ScholarPubMed
Chinnery, J. B. & Morris, D. L. (1986). Effects Of albendazole sulphoxide on viability of hydatid protoscoleces in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 815.CrossRefGoogle ScholarPubMed
Craig, P. S. (1994). Current research in echinococcosis. Parasitology Today 10, 209–211.CrossRefGoogle Scholar
Davis, A., Pawlowski, Z. S. & Dixon, H. (1986). Multicentre clinical trials of benzimidazolecarbamates in human echinococcosis. Bulletin of the World Health Organization 64, 383–386.Google ScholarPubMed
Delgado, G., Potkul, R. K., Treat, J. A., Lewandowski, G. S., Barter, J. F., Forst, D. & Rahman, A. (1989). A phase I/II study of intraperitoneally administered doxorubicin entrapped in cardiolipin liposomes in patients with ovarian cancer. American Journal of Obstetrics and Gynaecology 160, 812–817.CrossRefGoogle ScholarPubMed
Diekmann, H. W., Schneidereit, M. & Overbosch, D. (1989). Inhibitory effects of cimetidine ketoconazole and miconazole on the metabolism of praziquantel. Acta Leidensia 57, 217–228.Google Scholar
French, C. M. (1984). Mebendazole and surgery for human hydatid disease in Turkana. East African Medical Journal 61, 113–119.Google ScholarPubMed
Gabizon, A., Goren, D., Fuks, Z., Barenholz, A., Dagan, A. & Meshorer, A. (1983). Enhancement of adriamycin delivery to liver metastatic cells with increased tumoricidal effect using liposomes as drug carriers. Cancer Research 43, 4730–4735.Google ScholarPubMed
Gergoriadis, G. & Ryman, B. E. (1972). Fate of protein-containing liposomes injected into rats. An approach to treatment of storage diseases. European Journal of Biochemistry 24, 485–491.CrossRefGoogle Scholar
Heath, S., Chance, M. L. & New, R. R. C. (1984). Quantitative and ultrastructural studies on the uptake of drug loaded liposomes by mononuclear phagocytes infected with Leishmania donovani. Molecular and Biochemical Parasitology 12, 49–60.CrossRefGoogle ScholarPubMed
Hoaksey, P. E., Awadzi, K., Ward, S. A., Coventry, P. A., L'E, Orme M. & Edwards, G. (1991). Rapid and sensitive method for the determination of albendazole and albendazole sulphoxide in biological fluids. Journal of Chromatography 566, 224–249.CrossRefGoogle ScholarPubMed
Horton, R. J. (1989). Chemotherapy of Echinococcus infection in man with albendazole. Transactions of the Royal Society of Tropical Medicine and Hygiene 83, 97–102.CrossRefGoogle ScholarPubMed
Hrckova, G., Velebny, S. & Horak, J. (1993). A morphological study of the effects of liposomized albendazole on the muscle phase of Trichinella spiralis in mice. Journal of Helminthology 67, 24–30.CrossRefGoogle ScholarPubMed
Katare, O. P., Vyas, S. P. & Dixit, V. K. (1991). Proliposomes of indomethacin for oral administration. Journal of Microencapsulation 8, 1–7.CrossRefGoogle ScholarPubMed
Liance, M., Vuitton, D., Guerret-Stocker, S., Carbillet, J. P., Grimaud, J. A. & Houin, R. (1984). Experimental alveolar echinococcosis. Suitability of a murine model of intrahepatic infection by Echinococcus multilocularis for immunological studies. Experientia 40, 1436–1439.CrossRefGoogle ScholarPubMed
Luder, P. J., Siffert, B., Witassek, F., Meister, F. & Bircher, J. (1986). Treatment of hydatid disease with high oral doses of mebendazole. Long-term follow-up of plasma mebendazole levels and drug interactions. European Journal of Clinical Pharmacology 31, 443–448.CrossRefGoogle ScholarPubMed
Morris, D. L., Chinnery, J. B., Georgiou, G., Stamanakis, G. & Goelematis, B. (1987). Penetration of albendazole sulphoxide into hydatid cysts. Gut, 28, 75–80.CrossRefGoogle ScholarPubMed
New, R. R. C. (1990). Liposomes: A Practical Approach. IRL Press, Oxford University Press, Oxford.Google Scholar
New, R. R. C. (1994). Influence of liposome characteristics on their properties and fate. In Liposomes as Tools in Basic Research and Industry, (ed. Philipott, J. R. & Schuber, F.), pp. 3–20. CRC Press, Inc, Boca Raton, Florida, USA.Google Scholar
New, R. R. C., Chance, M. L. & Heath, S. (1981). The treatment of experimental cutaneous leishmaniasis with liposome-entrapped pentostam. Parasitology 83, 519–527.CrossRefGoogle Scholar
New, R. R. C., Chance, M. L., Thomas, S. C. & Peters, W. (1978). Antileishmanial activity of antimonials entrapped in liposomes. Nature, London 272, 55–56.CrossRefGoogle ScholarPubMed
New, R. R. C., Wen, H., Craig, P. S., Zou, P. F., Merdan, M., Wang, J. H., Wang, Y. H. & Zhang, J. H. (1994 b). Efficacy of albendazole administered orally is improved by encapsulation in liposomes, Journal of Controlled Release 28, 350–351.CrossRefGoogle Scholar
Roman, V., Bocquier, F., Leterrier, F. & Fatome, M. (1982). Action Radioprotectrice de la cysteamine encapsulee dans des liposomes administres par voie orate a la souris, Comptes Rendus de l'Académie des Sciences Paris 295, 191–193.Google Scholar
Saimot, A. G., Cremieux, A. C., Hay, J. M., Meulmans, A., Giovanangeli, M. D., Dlaitre, B. & Coulaud, J. P. (1983). Albendazole as a potential treatment for human hydatidosis. Lancet ii, 652–656.CrossRefGoogle Scholar
Schantz, P. M., Brandt, F. H., Dickson, C. M., Allen, C. R., Roberts, J. M. & Eberhard, M. L. (1990). Effects of albendazole on Echinococcus multilocularis infection in the Mongolian Jird. Journal of Infectious Diseases 162, 1403–1407.CrossRefGoogle ScholarPubMed
Sells, R. A., Owen, R. R., New, R. R. C. & Gilmore, I. T. (1987). Reduction in toxicity of doxorubicin by liposomal entrapment. Lancet 12, 624–625.CrossRefGoogle Scholar
Taylor, D. H., Morris, D. L., Richards, K. S. & Reffin, D. (1988). Echinococcus Multilocularis: in vivo results of therapy with albendazole and praziquantel. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 611–615.CrossRefGoogle ScholarPubMed
Todorov, T., Vutova, K., Mechkov, G., Georgiev, P., Kolev, K., Tonchev, Z. & Nedelkov, G. (1992). Chemotherapy of human cystic echinococcosis: Comparative efficacy of mebendazole and albendazole. Annals of Tropical Medicine and Parasitology 86, 59–66.CrossRefGoogle ScholarPubMed
Vanparijs, O. (1990). Chemotherapy of experimental Echinococcus multilocularis in jirds. Parasitology Resume 76, 238–240.CrossRefGoogle ScholarPubMed
Wang, J. H., Wen, H., Muhmut, M., New, R. R. C. & Craig, P. S. (1994). Determination of percentage of albendazole entrapped in liposomes and observation on liposomal albendazole by electronic microscopy. Acta Academiae Medicinae Xinjiang 16, 344–345.Google Scholar
Wen, H., Muhmut, M., Wang, J. H, New, R. R. C. & Craig, P. S. (1993 a). Pharmacokinetical study and determination of liposomal albendazole and its main metabolites by HPLC. Acta Academiae Medicinae Xinjiang 16, 214–220.Google Scholar
Wen, H., New, R. R. C. & Craig, P. S. (1993 b). Diagnosis and treatment of human hydatidosis. British Journal of Clinical Pharmacology 35, 565–574.CrossRefGoogle ScholarPubMed
Wen, H., Zhang, H. W., Muhmut, M., Zou, P. F., New, R. R. C. & Craig, P. S. (1994 a). Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis. Annals of Tropical Medicine and Parasitology, 88, 49–52.CrossRefGoogle ScholarPubMed
Wen, H., Zou, P. F., Yang, W. G., Lu, J., Wang, Y. H., Zhang, J. H., New, R. R. C. & Craig, P. S. (1994 b). Albendazole chemotherapy for human cystic and alveolar echinococcosis in northwestern China. Transactions of the Royal Society of Tropical Medicine and Hygiene 88, 340–343.Google Scholar
Wilson, J. F., Rausch, R. L., McMahon, B. J. & Schantz, P. M. (1992). Parasiticidal effect of chemotherapy in alveolar hydatid disease: review of experience with mebendazole and albendazole in Alaskan Eskimos. Clinical Infectious Diseases 15, 234–249.CrossRefGoogle ScholarPubMed
Yao, P. L., Fu, L. M., Xu, D. Z., Li, J., Ding, Z. X. & Chen, Q. G. (1985). Treatment of liver alveolar echinococcosis in Xinjiang Uygur Autonomous Region. Surgical Round 8, 65–68.Google Scholar
Zhang, H. W. & Wen, H. (1989). The determination of albendazole and its main metabolites in humans by HPLC. Chinese Journal of Clinical Pharmacology 5, 231–235.Google Scholar