Person:
Tejedor Jorge, Alberto

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First Name
Alberto
Last Name
Tejedor Jorge
URI
https://hdl.handle.net/20.500.14352/81678
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Medicina
Area
Medicina
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Author: Capilla, Javier × Subject: 663/665 ×

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    Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis
    (Antimicrobial Agents and Chemotherapy, 2018) López Sánchez, Alicia; Pérez Cantero, Alba; Torrado Salmerón, Carlos Félix; Martín Vicente, Adela; García Herrero, Víctor; González Nicolás González, María Ángeles; Lázaro Fernández, Alberto; Tejedor Jorge, Alberto; Torrado Durán, Santiago; García Rodríguez, Juan José; Capilla, Javier; Torrado Durán, Susana
    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.