Dod/amb: in Vivo Activity of a Novel Amb Formulation with Synthetic Cationic Bilayer Fragments

The ability of the versatile dioctadecyldimethylammonium bromide (DODAB), a bilayer-forming synthetic lipid previously shown to solubilize Amphotericin B (AMB), inspired this evaluation of in vivo activity of the DODAB/AMB formulation (DOD/AMB) against systemic candidiasis in a mouse model from survival and tissue burden experiments. AMB was simply added to a DODAB powder dispersion in water previously obtained by sonication with tip at concentrations ≤0.1 and 10 mg/mL, respectively, organic solvents completely absent. 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, causing disappearance of large water insoluble drug aggregates. From survival and tissue burden experiments, DOD/ AMB efficacy was equivalent to the one exhibited by Fungizone (DOC/AMB) -------100 and 70% survival respectively, at 0.4 mg/kg/day given i.p. for 10 days (P>0.05) --------, regarding elimination of Candida colonization in spleen and kidneys. In summary, DOD/AMB, was effective for treating systemic candidiasis in a mouse model.