Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis
| Autor: | Alberto Tejedor, Juan José García-Rodríguez, González-Nicolás Má, Carlos Torrado-Salmerón, Santiago Torrado-Santiago, Alba Pérez-Cantero, López-Sánchez A, Susana Torrado, García-Herrero, Alberto Lázaro, Adela Martin-Vicente, Javier Capilla |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Biodistribution Antifungal Agents efficacy 030106 microbiology Pharmacology Kidney Aspergillosis Nephrotoxicity Mice 03 medical and health sciences Amphotericin B Amphotericin B deoxycholate medicine Animals Experimental Therapeutics aspergillosis Pharmacology (medical) Lung Liposome Chemistry nephrotoxicity bacterial infections and mycoses medicine.disease amphotericin B Drug Combinations deoxycholate Infectious Diseases medicine.anatomical_structure pulmonary concentrations Pulmonary Aspergillosis Deoxycholic Acid medicine.drug |
| Zdroj: | Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00489-18 |
| Popis: | 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 represent a therapeutic advantage over liposomal commercial amphotericin B-based treatment of pulmonary aspergillosis. These results are encouraging to explore the usefulness of AMB:DCH 1:1.5 against this disease. |
| Databáze: | OpenAIRE |
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