期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 9, 期 -, 页码 2439-2458出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S58487
关键词
fungal infections; electrospinning; antifungals; controlled release; drug-matrix interactions
资金
- TCR Grant [R618/41/2008, R1054/69/2013]
- NRF-Technion [R-398-001-065592]
- A*STAR-BEP [R-265-000-437-305]
- Department of Mechanical Engineering, National University of Singapore, Singapore
Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections.
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