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Antimicrobial Agents and Chemotherapy, September 2004, p. 3246-3252, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3246-3252.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Treatment of Experimental Visceral Leishmaniasis with Amphotericin B in Stable Albumin Microspheres

J. A. Sánchez-Brunete,1 M. A. Dea,2 S. Rama,2 F. Bolás,2 J. M. Alunda,3 R. Raposo,4 M. T. Méndez,4 S. Torrado-Santiago,1 and J. J. Torrado1*

Department of Pharmacy and Pharmaceutical Technology,1 Department of Parasitology,2 Clinical Analysis School, Faculty of Pharmacy,4 Department of Animal Health, Faculty of Veterinary Medicine, Complutense University, Madrid, Spain3

Received 12 January 2004/ Returned for modification 26 April 2004/ Accepted 24 May 2004

Hydrophilic albumin microspheres are proposed as a new delivery system for amphotericin B (AMB; AMB microspheres). The acute toxicity of AMB microspheres was lower than that of the AMB-deoxycholate (AMB-Doc) reference formulation in hamsters. Lethal doses in healthy and infected animals were improved at least eight times. Intravenous bolus administration of doses of AMB microspheres up to 40 mg/kg of body weight did not produce acute symptoms of toxicity. The efficacy of this new formulation was tested against Leishmania infantum-infected hamsters at doses of 2, 10, 20, and 40 mg/kg. With the 2-mg/kg dose, the activity of AMB, as assessed through the parasite load reductions in the liver and spleen and the evolution of antibody levels, was also improved (P < 0.05) by use of the AMB microsphere system. At the higher doses of 10, 20, and 40 mg/kg, reductions in parasite levels of more than 99% were achieved in the liver and spleen after the administration of AMB microspheres. A pharmacokinetic study was performed to study the serum, liver, and spleen AMB concentrations after administration of AMB microspheres and the reference formulation. Interestingly, a significant accumulation of AMB in the spleen and liver was observed after AMB microsphere administration. Our results suggest that this new formulation is a promising alternative to the conventional AMB-Doc formulation for the treatment of visceral leishmaniasis.

* Corresponding author. Mailing address: Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain. Phone: 34 913941620. Fax: 34 913941736. E-mail: torrado1{at}farm.ucm.es.

Antimicrobial Agents and Chemotherapy, September 2004, p. 3246-3252, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3246-3252.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Espada, R., Valdespina, S., Dea, M. A., Molero, G., Ballesteros, M. P., Bolas, F., Torrado, J. J. (2008). In vivo distribution and therapeutic efficacy of a novel amphotericin B poly-aggregated formulation. J Antimicrob Chemother 61: 1125-1131 [Abstract] [Full Text]  
  • Rama Iniguez, S., Dea-Ayuela, M. A., Sanchez-Brunete, J. A., Torrado, J. J., Alunda, J. M., Bolas-Fernandez, F. (2006). Real-Time Reverse Transcription-PCR Quantification of Cytokine mRNA Expression in Golden Syrian Hamster Infected with Leishmania infantum and Treated with a New Amphotericin B Formulation.. Antimicrob. Agents Chemother. 50: 1195-1201 [Abstract] [Full Text]  
  • Al-Mohammed, H. I., Chance, M. L., Bates, P. A. (2005). Production and Characterization of Stable Amphotericin-Resistant Amastigotes and Promastigotes of Leishmania mexicana. Antimicrob. Agents Chemother. 49: 3274-3280 [Abstract] [Full Text]  


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