title: Design of Micelle Nanocontainers Based on PDMAEMA-b-PCL-b-PDMAEMA Triblock Copolymers for the Encapsulation of Amphotericin B.
abstract: The clinical application of amphotericin B (AmB), a broad spectrum antifungal agent, is limited by its poor solubility in aqueous medium and also by its proven renal toxicity. In this work, AmB was encapsulated in micelles obtained from the self-assembly of PDMAEMA-b-PCL-b-PDMAEMA triblock copolymers. The amount of encapsulated AmB depended on the copolymer composition, and short blocks of polycaprolactone (PCL) and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) showed better performance. All the studied formulations exhibited a controlled release of AmB along 150 h. The formulations presented reduced hemotoxicity while maintaining antifungal activities against Candida albicans, Candida krusei, and Candida glabrata comparable with free AmB. A reduction on the hemotoxicity was found to be due to the slow release and subsequent low aggregation achieved with the use of polymer micelle nanocontainers.
authors: Departamento de Química, Pontificia Universidad Javeriana, Carrera 7 No. 40-62, Bogotá D.C., Colombia.
authors: Ivonne L
authors: IL
authors: Diaz
authors: Departamento de Microbiología, Pontificia Universidad Javeriana, Carrera 7 No. 40-62, Bogotá D.C., Colombia.
authors: Claudia
authors: C
authors: Parra
authors: Departamento de Microbiología, Pontificia Universidad Javeriana, Carrera 7 No. 40-62, Bogotá D.C., Colombia.
authors: Melva
authors: M
authors: Linarez
authors: Departamento de Química, Universidad Nacional de Colombia, Carrera 45 No. 26-85, edificio 451 of. 449, Bogotá D.C., Colombia. ldperezp@unal.edu.co.
authors: Leon D
authors: LD
authors: Perez
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D002175:Candida / Q000187:drug effects / Q000254:growth & development; D002208:Caproates / Q000138:chemical synthesis* / Q000633:toxicity; D003692:Delayed-Action Preparations; D052978:Disk Diffusion Antimicrobial Tests; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008689:Methacrylates / Q000138:chemical synthesis* / Q000633:toxicity; D008823:Micelles; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods; D011108:Polymers / Q000138:chemical synthesis* / Q000633:toxicity; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D002208:Caproates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008689:Methacrylates; D008823:Micelles; C000612081:PDMAEMA-b-PCL-b-PDMAEMA; D011108:Polymers; D000666:Amphotericin B
keywords: amphotericin B; antifungal agent; hemotoxicity; micelles