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AAPS PharmSciTech ; 18(6): 1917-1924, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27858252

RESUMO

We report the successful implementation of a novel melt co-extrusion process to fabricate ca. 1 µm diameter fibers of poly(caprolactone) (PCL) containing the antifungal compound clotrimazole in concentrations between 4 and 8 wt%. The process involves co-extrusion of a clotrimazole-loaded PCL along with poly(ethylene oxide) (PEO) as a co-feed, with subsequent removal of PEO to isolate PCL-clotrimazole fibers. In vitro tests of the clotrimazole-containing fibers against the fungus Aspergillus fumigatus, Candida albicans, and Trichophyton mentagrophytes strains demonstrated good antifungal activity which was maintained for more than 3 weeks. An in vivo study using a mouse model showed the lowest tissue fungal burden for PCL-clotrimazole when compared to a PCL-only patch and untreated controls. Comparative studies were conducted with clotrimazole-containing PCL fibers fabricated by electrospinning. Our data showed that the co-extruded, clotrimazole-containing fibers maintain activity for longer times vs. electrospun samples. This, coupled with the much higher throughput of the co-extrusion process vs. electrospinning, renders this new approach very attractive for the fabrication of drug-releasing polymer fibers.


Assuntos
Antifúngicos/química , Química Farmacêutica/métodos , Nanofibras/química , Polímeros/química , Animais , Antifúngicos/farmacocinética , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Caproatos/química , Caproatos/farmacocinética , Clotrimazol/química , Clotrimazol/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos/efeitos dos fármacos , Liberação Controlada de Fármacos/fisiologia , Lactonas/química , Lactonas/farmacocinética , Camundongos , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polímeros/farmacocinética , Trichophyton/efeitos dos fármacos , Trichophyton/metabolismo
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