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

Identifier:  imarina:3872419

Handle: https://hdl.handle.net/20.500.11797/imarina3872419

Authors:  López-Sánchez, A; Pérez-Cantero, A; Torrado-Salmerón, C; Martin-Vicente, A; García-Herrero, V; González-Nicolás, MA; Lázaro, A; Tejedor, A; Torrado-Santiago, S; García-Rodríguez, JJ; Capilla, J; Torrado, S

Abstract:
An experimental micellar formulation of amphotericin B (AMB) with sodium deoxycholate (DCH), AMB:DCH 1:1.5, was obtained and characterized to determine its aggregation state and particle size. Biodistribution, nephrotoxicity and efficacy against pulmonary aspergillosis in a murine model were studied and compared to the liposomal commercial 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) compared to 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 morphology and particle size. The efficacy study has shown that both drugs administered at 5 mg/kg produced similar survival percentages and reduction of fungal burden. A slightly lower nephrotoxicity, associated to 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 that could represents a therapeutic advantage over liposomal commercial amphotericin B-based treatment of pulmonary aspergillosis. These results are encouraging to explore the AMB:DCH 1:1.5 usefulness against this disease.Copyright © 2018 American Society for Microbiology.