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Design of Micelle Nanocontainers Based on PDMAEMA-b-PCL-b-PDMAEMA Triblock Copolymers for the Encapsulation of Amphotericin B

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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.

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ACKNOWLEDGEMENTS

The authors thank to the Pontificia Universidad Javeriana for the financial support throught the grant number 5620.

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Authors and Affiliations

  1. Departamento de Química, Pontificia Universidad Javeriana, Carrera 7 No. 40-62, Bogotá D.C., Colombia

    Ivonne L. Diaz

  2. Departamento de Microbiología, Pontificia Universidad Javeriana, Carrera 7 No. 40-62, Bogotá D.C., Colombia

    Claudia Parra & Melva Linarez

  3. Departamento de Química, Universidad Nacional de Colombia, Carrera 45 No. 26-85, edificio 451 of. 449, Bogotá D.C., Colombia

    Leon D. Perez

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  1. Ivonne L. Diaz
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Correspondence to Leon D. Perez.

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Diaz, I.L., Parra, C., Linarez, M. et al. Design of Micelle Nanocontainers Based on PDMAEMA-b-PCL-b-PDMAEMA Triblock Copolymers for the Encapsulation of Amphotericin B. AAPS PharmSciTech 16, 1069–1078 (2015). https://doi.org/10.1208/s12249-015-0298-9

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