JAC Advance Access published online on August 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg383
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Departamento de Análises
Clínicas, Faculdade de Ciências Farmacêuticas,
Universidade de São Paulo;
* Corresponding author. E-mail: mcribeir{at}iq.usp.br.
Received 6 September 2002
; 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 (
Keywords: drug delivery, amphotericin B, in
vivo
In vivo activity of a novel amphotericin
B formulation with synthetic cationic bilayer fragments
2 Departamento de Bioquímica, Instituto
de Química, Universidade de São Paulo, CP 26077,
CEP 05513-970 São Paulo, Brazil
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.
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