Limits...
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.

Show MeSH

Related in: MedlinePlus

Scanning electron micrographs showing the electrospun gelatin fibers loaded with various antifungals. (A) No antifungals; (B) amphotericin B; (C) natamycin; (D) fluconazole; (E) itraconazole; (F) terbinafine. (G) Histogram showing the effects of various antifungals on the average fiber diameter.Notes: ***P<0.001; scale bar =50 μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4043707&req=5

f2-ijn-9-2439: Scanning electron micrographs showing the electrospun gelatin fibers loaded with various antifungals. (A) No antifungals; (B) amphotericin B; (C) natamycin; (D) fluconazole; (E) itraconazole; (F) terbinafine. (G) Histogram showing the effects of various antifungals on the average fiber diameter.Notes: ***P<0.001; scale bar =50 μm.

Mentions: Gelatin and antifungal-loaded gelatin fiber mats were electrospun from trifluoroethanol solution and their antifungal activities were evaluated. After an initial optimization, 10% w/v of gelatin was used and the final antifungal concentration was maintained at 0.25% weight/weight (w/w) in order to minimize bead formation. Figure 2A–F show the morphology of gelatin and various antifungal-loaded gelatin fibers imaged after glutaraldehyde crosslinking. The images show smooth surface and absence of any beading, pores, or physical defects in various antifungal loaded fiber mats. The average diameters of individual fibers in various antifungal-loaded mats are shown in Figure 2G. Fiber mats without antifungals had a mean diameter of 0.8±0.4 μm. The average diameters of the individual fibers in both the polyene antifungal-loaded mats had a larger and broader diameter distribution compared to the other antifungal-loaded mats (P<0.001). For the two polyene-loaded mats, the average diameters of the fibers remained higher for natamycin (1.8±1.0 μm) compared to amphotericin B (1.4±0.9 μm). For electrospun gelatin, an increase in diameter was observed with an increasing concentration of gelatin or solvent composition.36 In the absence of these parameters, the above results indicate significant interactions between the polyenes and gelatin matrix. Among the two azoles, addition of fluconazole did not affect the diameter distribution of the fibers (0.8±0.4 μm), whereas incorporation of itraconazole increased the diameter moderately (1.2±0.6 μm). The average diameter of terbinafine-loaded fibers (1.4±0.6 μm) was larger compared to the control 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)

Scanning electron micrographs showing the electrospun gelatin fibers loaded with various antifungals. (A) No antifungals; (B) amphotericin B; (C) natamycin; (D) fluconazole; (E) itraconazole; (F) terbinafine. (G) Histogram showing the effects of various antifungals on the average fiber diameter.Notes: ***P<0.001; scale bar =50 μm.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-9-2439: Scanning electron micrographs showing the electrospun gelatin fibers loaded with various antifungals. (A) No antifungals; (B) amphotericin B; (C) natamycin; (D) fluconazole; (E) itraconazole; (F) terbinafine. (G) Histogram showing the effects of various antifungals on the average fiber diameter.Notes: ***P<0.001; scale bar =50 μm.
Mentions: Gelatin and antifungal-loaded gelatin fiber mats were electrospun from trifluoroethanol solution and their antifungal activities were evaluated. After an initial optimization, 10% w/v of gelatin was used and the final antifungal concentration was maintained at 0.25% weight/weight (w/w) in order to minimize bead formation. Figure 2A–F show the morphology of gelatin and various antifungal-loaded gelatin fibers imaged after glutaraldehyde crosslinking. The images show smooth surface and absence of any beading, pores, or physical defects in various antifungal loaded fiber mats. The average diameters of individual fibers in various antifungal-loaded mats are shown in Figure 2G. Fiber mats without antifungals had a mean diameter of 0.8±0.4 μm. The average diameters of the individual fibers in both the polyene antifungal-loaded mats had a larger and broader diameter distribution compared to the other antifungal-loaded mats (P<0.001). For the two polyene-loaded mats, the average diameters of the fibers remained higher for natamycin (1.8±1.0 μm) compared to amphotericin B (1.4±0.9 μm). For electrospun gelatin, an increase in diameter was observed with an increasing concentration of gelatin or solvent composition.36 In the absence of these parameters, the above results indicate significant interactions between the polyenes and gelatin matrix. Among the two azoles, addition of fluconazole did not affect the diameter distribution of the fibers (0.8±0.4 μm), whereas incorporation of itraconazole increased the diameter moderately (1.2±0.6 μm). The average diameter of terbinafine-loaded fibers (1.4±0.6 μm) was larger compared to the control 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