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Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats.

Lakshminarayanan R, Sridhar R, Loh XJ, Nandhakumar M, Barathi VA, Kalaipriya M, Kwan JL, Liu SP, Beuerman RW, Ramakrishna S - Int J Nanomedicine (2014)

Bottom Line: 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.As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes.

View Article: PubMed Central - PubMed

Affiliation: Singapore Eye Research Institute, Singapore ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore.

ABSTRACT
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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Efficacy of drug-loaded gelatin fiber mats against filamentous fungi. The antifungal activity against Aspergillus and Fusarium strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (***P<0.001 compared to Aspergillus brasiliensis ATCC 16404); (B) natamycin (*P<0.05 compared to Fusarium solani ATCC 3636 strains; @P<0.05 compared to A. brasiliensis ATCC 16404 strains); (C) terbinafine (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to A. brasiliensis ATCC 16404); (D) itraconazole (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to F. solani ATCC 26671 strains; #P<0.05 compared to A. fumigatus ATCC 90906 strains); and (E) fluconazole. (F) Representative photographs showing the zone of inhibition of gelatin (upper panel) and amphotericin B-loaded gelatin (lower panels) fiber mats.Note: The absence of bars in the graph indicates no inhibition against the particular strain.Abbreviation: ATCC, American Tissue Culture Collection.
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f4-ijn-9-2439: Efficacy of drug-loaded gelatin fiber mats against filamentous fungi. The antifungal activity against Aspergillus and Fusarium strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (***P<0.001 compared to Aspergillus brasiliensis ATCC 16404); (B) natamycin (*P<0.05 compared to Fusarium solani ATCC 3636 strains; @P<0.05 compared to A. brasiliensis ATCC 16404 strains); (C) terbinafine (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to A. brasiliensis ATCC 16404); (D) itraconazole (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to F. solani ATCC 26671 strains; #P<0.05 compared to A. fumigatus ATCC 90906 strains); and (E) fluconazole. (F) Representative photographs showing the zone of inhibition of gelatin (upper panel) and amphotericin B-loaded gelatin (lower panels) fiber mats.Note: The absence of bars in the graph indicates no inhibition against the particular strain.Abbreviation: ATCC, American Tissue Culture Collection.

Mentions: The in vitro antifungal activities of the fiber mats were determined against four filamentous pathogens as well. As was observed before, both the polyene antifungals inhibited the growth of all four filamentous fungi (Figure 4A and B). Itraconazole-loaded fiber mats showed strong inhibition for two Aspergillus strains, whereas fluconazole-loaded fiber mats had no activity against all the filamentous pathogens tested (Figure 4D and E). Of all the antifungals, terbinafine chloride-loaded fiber mats displayed the strongest inhibitory activity against filamentous fungal species (Figure 4C). These results suggest that polyene-loaded fiber mats retained the broad-spectrum antifungal properties, whereas terbinafine chloride-loaded fiber mats were effective against filamentous fungi. Among the two azoles, itraconazole-loaded fiber mats were superior compared to fluconazole-loaded fiber mats.


Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats.

Lakshminarayanan R, Sridhar R, Loh XJ, Nandhakumar M, Barathi VA, Kalaipriya M, Kwan JL, Liu SP, Beuerman RW, Ramakrishna S - Int J Nanomedicine (2014)

Efficacy of drug-loaded gelatin fiber mats against filamentous fungi. The antifungal activity against Aspergillus and Fusarium strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (***P<0.001 compared to Aspergillus brasiliensis ATCC 16404); (B) natamycin (*P<0.05 compared to Fusarium solani ATCC 3636 strains; @P<0.05 compared to A. brasiliensis ATCC 16404 strains); (C) terbinafine (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to A. brasiliensis ATCC 16404); (D) itraconazole (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to F. solani ATCC 26671 strains; #P<0.05 compared to A. fumigatus ATCC 90906 strains); and (E) fluconazole. (F) Representative photographs showing the zone of inhibition of gelatin (upper panel) and amphotericin B-loaded gelatin (lower panels) fiber mats.Note: The absence of bars in the graph indicates no inhibition against the particular strain.Abbreviation: ATCC, American Tissue Culture Collection.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043707&req=5

f4-ijn-9-2439: Efficacy of drug-loaded gelatin fiber mats against filamentous fungi. The antifungal activity against Aspergillus and Fusarium strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (***P<0.001 compared to Aspergillus brasiliensis ATCC 16404); (B) natamycin (*P<0.05 compared to Fusarium solani ATCC 3636 strains; @P<0.05 compared to A. brasiliensis ATCC 16404 strains); (C) terbinafine (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to A. brasiliensis ATCC 16404); (D) itraconazole (***P<0.001 compared to F. solani ATCC 3636 strains; @@@P<0.001 compared to F. solani ATCC 26671 strains; #P<0.05 compared to A. fumigatus ATCC 90906 strains); and (E) fluconazole. (F) Representative photographs showing the zone of inhibition of gelatin (upper panel) and amphotericin B-loaded gelatin (lower panels) fiber mats.Note: The absence of bars in the graph indicates no inhibition against the particular strain.Abbreviation: ATCC, American Tissue Culture Collection.
Mentions: The in vitro antifungal activities of the fiber mats were determined against four filamentous pathogens as well. As was observed before, both the polyene antifungals inhibited the growth of all four filamentous fungi (Figure 4A and B). Itraconazole-loaded fiber mats showed strong inhibition for two Aspergillus strains, whereas fluconazole-loaded fiber mats had no activity against all the filamentous pathogens tested (Figure 4D and E). Of all the antifungals, terbinafine chloride-loaded fiber mats displayed the strongest inhibitory activity against filamentous fungal species (Figure 4C). These results suggest that polyene-loaded fiber mats retained the broad-spectrum antifungal properties, whereas terbinafine chloride-loaded fiber mats were effective against filamentous fungi. Among the two azoles, itraconazole-loaded fiber mats were superior compared to fluconazole-loaded fiber mats.

Bottom Line: 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.As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes.

View Article: PubMed Central - PubMed

Affiliation: Singapore Eye Research Institute, Singapore ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus