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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 yeast strains. The antifungal activity against Candida albicans strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (*P<0.05 compared to C. albicans ATCC 10231 strains; **P<0.01 compared to C. albicans ATCC 10231 strains; @@P<0.01 compared to C. albicans ATCC 2091 strains; @@@P<0.001 compared to C. albicans ATCC 2091 strains; #P<0.05 compared to C. albicans ATCC 24433); (B) natamycin (*P<0.05 compared to C. albicans ATCC 10231 strains); (C) terbinafine (***P<0.001 compared to all the groups); (D) itraconazole (***P<0.01 compared to all the groups except C. albicans ATCC 24433 strains; @@@P<0.001 compared to all the groups except C. albicans ATCC 2091 strains); and (E) fluconazole. ***P<0.001 compared to all the groups. (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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f3-ijn-9-2439: Efficacy of drug-loaded gelatin fiber mats against yeast strains. The antifungal activity against Candida albicans strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (*P<0.05 compared to C. albicans ATCC 10231 strains; **P<0.01 compared to C. albicans ATCC 10231 strains; @@P<0.01 compared to C. albicans ATCC 2091 strains; @@@P<0.001 compared to C. albicans ATCC 2091 strains; #P<0.05 compared to C. albicans ATCC 24433); (B) natamycin (*P<0.05 compared to C. albicans ATCC 10231 strains); (C) terbinafine (***P<0.001 compared to all the groups); (D) itraconazole (***P<0.01 compared to all the groups except C. albicans ATCC 24433 strains; @@@P<0.001 compared to all the groups except C. albicans ATCC 2091 strains); and (E) fluconazole. ***P<0.001 compared to all the groups. (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 antifungal properties of drug-loaded fiber mats were evaluated by radial disc diffusion assay against a panel of C. albicans, and the zone of inhibition was measured (Figures S1–S7). Figure 3 shows the activity of antifungal-loaded fiber mats (expressed as the zone of inhibition) against various C. albicans strains. The results suggest that the antifungal activity depends on the type of antifungals loaded. Polyene-loaded fiber mats displayed excellent antifungal properties, suppressing the growth of both the American Type Culture Collection (Manassas, VA, USA) and the clinical isolates of C. albicans (Figure 3A and B). The other antifungal-loaded fiber mats displayed significant variability in anti-Candida activity. Fluconazole- and terbinafine-loaded fiber mats were the least effective as they showed clear zone of inhibition against only one strain of C. albicans (Figure 3C and D). Itraconazole-loaded fiber mats, on the other hand, inhibited the growth of two American Type Culture Collection strains of C. albicans and a weaker inhibitory activity against the other three strains (Figure 3E).


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 yeast strains. The antifungal activity against Candida albicans strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (*P<0.05 compared to C. albicans ATCC 10231 strains; **P<0.01 compared to C. albicans ATCC 10231 strains; @@P<0.01 compared to C. albicans ATCC 2091 strains; @@@P<0.001 compared to C. albicans ATCC 2091 strains; #P<0.05 compared to C. albicans ATCC 24433); (B) natamycin (*P<0.05 compared to C. albicans ATCC 10231 strains); (C) terbinafine (***P<0.001 compared to all the groups); (D) itraconazole (***P<0.01 compared to all the groups except C. albicans ATCC 24433 strains; @@@P<0.001 compared to all the groups except C. albicans ATCC 2091 strains); and (E) fluconazole. ***P<0.001 compared to all the groups. (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

f3-ijn-9-2439: Efficacy of drug-loaded gelatin fiber mats against yeast strains. The antifungal activity against Candida albicans strains is expressed as the zone of inhibition measured by radial diffusion assay. Fiber mats loaded with (A) amphotericin B (*P<0.05 compared to C. albicans ATCC 10231 strains; **P<0.01 compared to C. albicans ATCC 10231 strains; @@P<0.01 compared to C. albicans ATCC 2091 strains; @@@P<0.001 compared to C. albicans ATCC 2091 strains; #P<0.05 compared to C. albicans ATCC 24433); (B) natamycin (*P<0.05 compared to C. albicans ATCC 10231 strains); (C) terbinafine (***P<0.001 compared to all the groups); (D) itraconazole (***P<0.01 compared to all the groups except C. albicans ATCC 24433 strains; @@@P<0.001 compared to all the groups except C. albicans ATCC 2091 strains); and (E) fluconazole. ***P<0.001 compared to all the groups. (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 antifungal properties of drug-loaded fiber mats were evaluated by radial disc diffusion assay against a panel of C. albicans, and the zone of inhibition was measured (Figures S1–S7). Figure 3 shows the activity of antifungal-loaded fiber mats (expressed as the zone of inhibition) against various C. albicans strains. The results suggest that the antifungal activity depends on the type of antifungals loaded. Polyene-loaded fiber mats displayed excellent antifungal properties, suppressing the growth of both the American Type Culture Collection (Manassas, VA, USA) and the clinical isolates of C. albicans (Figure 3A and B). The other antifungal-loaded fiber mats displayed significant variability in anti-Candida activity. Fluconazole- and terbinafine-loaded fiber mats were the least effective as they showed clear zone of inhibition against only one strain of C. albicans (Figure 3C and D). Itraconazole-loaded fiber mats, on the other hand, inhibited the growth of two American Type Culture Collection strains of C. albicans and a weaker inhibitory activity against the other three strains (Figure 3E).

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