Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis

Antimicrobial Agents and Chemotherapy
Alicia López-SánchezSusana Torrado

Abstract

An experimental micellar formulation of 1:1.5 amphotericin B-sodium deoxycholate (AMB:DCH 1:1.5) was obtained and characterized to determine its aggregation state and particle size. The biodistribution, nephrotoxicity, and efficacy against pulmonary aspergillosis in a murine model were studied and compared to the liposomal commercial formulation of amphotericin B after intravenous administration. The administration of 5 mg/kg AMB:DCH 1:1.5 presented 2.8-fold-higher lung concentrations (18.125 ± 3.985 μg/g after 6 daily doses) and lower kidney exposure (0.391 ± 0.167 μg/g) than liposomal commercial amphotericin B (6.567 ± 1.536 and 5.374 ± 1.157 μg/g in lungs and kidneys, respectively). The different biodistribution of AMB:DCH micelle systems compared to liposomal commercial amphotericin B was attributed to their different morphologies and particle sizes. The efficacy study has shown that both drugs administered at 5 mg/kg produced similar survival percentages and reductions of fungal burden. A slightly lower nephrotoxicity, associated with amphotericin B, was observed with AMB:DCH 1:1.5 than the one induced by the liposomal commercial formulation. However, AMB:DCH 1:1.5 reached higher AMB concentrations in lungs, which could re...Continue Reading

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Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.