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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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Cytotoxicity of polyene-loaded antifungal fiber mats against (A) human corneal and (B) human sclera fibroblasts. XL-gelatin fiber mat is the gelatin crosslinked with glutaraldehyde for 24 hours. For amphotericin B- and natamycin-loaded fiber mats the crosslinking time was 3 hours.Notes: *P<0.05 compared to XL-gelatin fiber mats; **P<0.01 compared to XL-gelatin fiber mats; @P<0.05 compared to control.Abbreviation: AmpB, amphotericin B.
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f10-ijn-9-2439: Cytotoxicity of polyene-loaded antifungal fiber mats against (A) human corneal and (B) human sclera fibroblasts. XL-gelatin fiber mat is the gelatin crosslinked with glutaraldehyde for 24 hours. For amphotericin B- and natamycin-loaded fiber mats the crosslinking time was 3 hours.Notes: *P<0.05 compared to XL-gelatin fiber mats; **P<0.01 compared to XL-gelatin fiber mats; @P<0.05 compared to control.Abbreviation: AmpB, amphotericin B.

Mentions: The biocompatibility of polyene-loaded antifungals was evaluated by monitoring the cell viability of human corneal fibroblasts and human sclera fibroblasts primary cells. For a comparison we have also determined the cytotoxicity of free polyenes with human corneal fibroblast cells (Figure 10A). At 10 μg/mL, both natamycin and amphotericin B did not show significant cytotoxicity to the human corneal fibroblasts. Gelatin gels without glutaraldehyde crosslinking also did not show any toxicity. However, 24-hour glutaraldehyde crosslinked gelatin fiber mats displayed significant toxicity. Natamycin-loaded fiber mats displayed better compatibility with the human corneal fibroblasts (~90% viable cells) compared to amphotericin B-loaded fiber mats (~67% viable cells). However, for primary human sclera fibroblasts, both the antifungal-loaded fiber mats were equally less toxic (~70% viable cells; Figure 10B). These results indicate excellent biocompatibility of fiber mats with human fibroblasts.


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)

Cytotoxicity of polyene-loaded antifungal fiber mats against (A) human corneal and (B) human sclera fibroblasts. XL-gelatin fiber mat is the gelatin crosslinked with glutaraldehyde for 24 hours. For amphotericin B- and natamycin-loaded fiber mats the crosslinking time was 3 hours.Notes: *P<0.05 compared to XL-gelatin fiber mats; **P<0.01 compared to XL-gelatin fiber mats; @P<0.05 compared to control.Abbreviation: AmpB, amphotericin B.
© Copyright Policy
Related In: Results  -  Collection

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

f10-ijn-9-2439: Cytotoxicity of polyene-loaded antifungal fiber mats against (A) human corneal and (B) human sclera fibroblasts. XL-gelatin fiber mat is the gelatin crosslinked with glutaraldehyde for 24 hours. For amphotericin B- and natamycin-loaded fiber mats the crosslinking time was 3 hours.Notes: *P<0.05 compared to XL-gelatin fiber mats; **P<0.01 compared to XL-gelatin fiber mats; @P<0.05 compared to control.Abbreviation: AmpB, amphotericin B.
Mentions: The biocompatibility of polyene-loaded antifungals was evaluated by monitoring the cell viability of human corneal fibroblasts and human sclera fibroblasts primary cells. For a comparison we have also determined the cytotoxicity of free polyenes with human corneal fibroblast cells (Figure 10A). At 10 μg/mL, both natamycin and amphotericin B did not show significant cytotoxicity to the human corneal fibroblasts. Gelatin gels without glutaraldehyde crosslinking also did not show any toxicity. However, 24-hour glutaraldehyde crosslinked gelatin fiber mats displayed significant toxicity. Natamycin-loaded fiber mats displayed better compatibility with the human corneal fibroblasts (~90% viable cells) compared to amphotericin B-loaded fiber mats (~67% viable cells). However, for primary human sclera fibroblasts, both the antifungal-loaded fiber mats were equally less toxic (~70% viable cells; Figure 10B). These results indicate excellent biocompatibility of fiber mats with human fibroblasts.

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