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JAC Advance Access originally published online on August 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 412-418
© 2003 The British Society for Antimicrobial Chemotherapy

In vivo activity of a novel amphotericin B formulation with synthetic cationic bilayer fragments

Nilton Lincopan1, Elsa M. Mamizuka1 and Ana M. Carmona-Ribeiro2,*

1 Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo; 2 Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05513-970 São Paulo, Brazil

Received 6 September 2002; returned 25 January 2003; revised 12 May 2003; accepted 15 June 2003

Solubilization of amphotericin B (AMB) by dioctadecyldimethylammonium bromide (DODAB) bilayer fragments inspired this evaluation of its in vivo activity from survival and tissue burden experiments against systemic candidiasis in a mouse model. AMB (<=0.1 g/L) was simply added to a DODAB powder dispersion in water (10 g/L) previously prepared by sonication in the absence of organic solvents. The AMB aggregation state was evaluated from UV–visible light absorption and dynamic light scattering for aggregate sizing. AMB was stabilized by the DODAB bilayer fragments in its monomeric form, mixing of AMB and DODAB dispersion in pure water causing disappearance of large water-insoluble drug aggregates. From survival experiments, both the bilayer, DODAB/AMB, and the traditional deoxycholate/AMB formulation (DOC/AMB) had identical effect when given by the same route at the same dose of 0.4 mg/kg/day given intraperitoneally for 10 days. From spleen and kidneys tissue burden experiments, similar efficacy of both preparations in reducing tissue cfu counts was obtained. In summary, DODAB/AMB was as effective as DOC/AMB for treating systemic candidiasis in a mouse model.

Keywords: drug delivery, amphotericin B, in vivo

* Corresponding author. Tel: +55-11-30912164; Fax: +55-11-30915579; E-mail: mcribeir{at}iq.usp.br


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