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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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Related in: MedlinePlus

(A) Candidacidal properties of the fiber mats loaded with amphotericin B and natamycin. (B) Kinetics of candidacidal action of amphotericin B and natamycin-loaded fiber mats.Notes: There was a significant decrease in the viability of Candida albicans exposed to antifungal-loaded fiber mats; **P<0.01.Abbreviation: AmpB, amphotericin B.
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f6-ijn-9-2439: (A) Candidacidal properties of the fiber mats loaded with amphotericin B and natamycin. (B) Kinetics of candidacidal action of amphotericin B and natamycin-loaded fiber mats.Notes: There was a significant decrease in the viability of Candida albicans exposed to antifungal-loaded fiber mats; **P<0.01.Abbreviation: AmpB, amphotericin B.

Mentions: Since both the polyene-loaded fiber mats displayed generally good inhibitory activity, the remaining experiments were performed with amphotericin B- and natamycin-loaded fiber mats. After incubation for 52 hours, both the polyene-loaded fiber mats resulted in considerable loss of viability (≥2 log reduction in viability) of C. albicans (Figure 6A), suggesting potent candidacidal action. To gain further insights, the kinetics of candidacidal action after exposing C. albicans (1.5×105 CFU/mL) to amphotericin B- or natamycin-loaded fiber mats was also investigated (Figure 6B). At various time intervals, the supernatant was diluted (102 or 103 fold), plated on Sabouraud dextrose agar, and the number of yeast colonies was counted after 48 hours. For both the polyene antifungal-loaded fiber mats, a steep decrease in the viability of C. albicans was observed during early incubation time. After 24 hours of incubation, amphotericin B-loaded fiber mats caused 1.6 log10 CFU/mL decrease (97.3% killing), whereas natamycin caused 1.2 log log10 CFU/mL decrease (93% killing) in the viability of C. albicans.


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)

(A) Candidacidal properties of the fiber mats loaded with amphotericin B and natamycin. (B) Kinetics of candidacidal action of amphotericin B and natamycin-loaded fiber mats.Notes: There was a significant decrease in the viability of Candida albicans exposed to antifungal-loaded fiber mats; **P<0.01.Abbreviation: AmpB, amphotericin B.
© Copyright Policy
Related In: Results  -  Collection

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

f6-ijn-9-2439: (A) Candidacidal properties of the fiber mats loaded with amphotericin B and natamycin. (B) Kinetics of candidacidal action of amphotericin B and natamycin-loaded fiber mats.Notes: There was a significant decrease in the viability of Candida albicans exposed to antifungal-loaded fiber mats; **P<0.01.Abbreviation: AmpB, amphotericin B.
Mentions: Since both the polyene-loaded fiber mats displayed generally good inhibitory activity, the remaining experiments were performed with amphotericin B- and natamycin-loaded fiber mats. After incubation for 52 hours, both the polyene-loaded fiber mats resulted in considerable loss of viability (≥2 log reduction in viability) of C. albicans (Figure 6A), suggesting potent candidacidal action. To gain further insights, the kinetics of candidacidal action after exposing C. albicans (1.5×105 CFU/mL) to amphotericin B- or natamycin-loaded fiber mats was also investigated (Figure 6B). At various time intervals, the supernatant was diluted (102 or 103 fold), plated on Sabouraud dextrose agar, and the number of yeast colonies was counted after 48 hours. For both the polyene antifungal-loaded fiber mats, a steep decrease in the viability of C. albicans was observed during early incubation time. After 24 hours of incubation, amphotericin B-loaded fiber mats caused 1.6 log10 CFU/mL decrease (97.3% killing), whereas natamycin caused 1.2 log log10 CFU/mL decrease (93% killing) in the viability of C. albicans.

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