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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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Chemical structures of antifungals used in this study. (A) Amphotericin B; (B) natamycin; (C) fluconazole; (D) itraconazole; (E) terbinafine chloride.
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f1-ijn-9-2439: Chemical structures of antifungals used in this study. (A) Amphotericin B; (B) natamycin; (C) fluconazole; (D) itraconazole; (E) terbinafine chloride.

Mentions: In terms of mechanism of action, the available antifungals can be grouped into three categories: 1) polyene, azole, and allylamine antifungals that target ergosterol or ergosterol biosynthetic pathways; 2) echinocandins, which are β-glucan synthase inhibitors; and 3) fluoropyrimidines, which target RNA synthesis. Due to its inherent biodegradability under physiological environments and nonimmunogenic properties, gelatin is used in numerous food and cosmetic applications as well as in cell-compatible biomaterials.34,35 Using appropriate solvent composition, electrospinning has been used to generate gelatin fibers with a wide range of diameters.36 In this study, the efficacy of polyene, azole, and allylamine antifungal drugs (Figure 1) incorporated into gelatin fiber mats against various yeasts/fungal pathogens were evaluated, their fungicidal kinetics were tested, and their toxicity on primary fibroblast cells was assessed. The interaction between drugs and gelatin was investigated by circular dichroism (CD) and rheological studies.


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)

Chemical structures of antifungals used in this study. (A) Amphotericin B; (B) natamycin; (C) fluconazole; (D) itraconazole; (E) terbinafine chloride.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-9-2439: Chemical structures of antifungals used in this study. (A) Amphotericin B; (B) natamycin; (C) fluconazole; (D) itraconazole; (E) terbinafine chloride.
Mentions: In terms of mechanism of action, the available antifungals can be grouped into three categories: 1) polyene, azole, and allylamine antifungals that target ergosterol or ergosterol biosynthetic pathways; 2) echinocandins, which are β-glucan synthase inhibitors; and 3) fluoropyrimidines, which target RNA synthesis. Due to its inherent biodegradability under physiological environments and nonimmunogenic properties, gelatin is used in numerous food and cosmetic applications as well as in cell-compatible biomaterials.34,35 Using appropriate solvent composition, electrospinning has been used to generate gelatin fibers with a wide range of diameters.36 In this study, the efficacy of polyene, azole, and allylamine antifungal drugs (Figure 1) incorporated into gelatin fiber mats against various yeasts/fungal pathogens were evaluated, their fungicidal kinetics were tested, and their toxicity on primary fibroblast cells was assessed. The interaction between drugs and gelatin was investigated by circular dichroism (CD) and rheological studies.

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