Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 52, Issue 3, Pages 412-418Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkg383
Keywords
drug delivery; amphotericin B; in vivo
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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 (less than or equal to0.1 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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