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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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Cumulative release profile of antifungals form gelatin fiber mats.
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f5-ijn-9-2439: Cumulative release profile of antifungals form gelatin fiber mats.

Mentions: The cumulative release profile for various antifungals was determined by UV spectrophotometry (Figure 5). The amount of antifungals released is expressed as μg/mg of fiber mats. The release profile was similar for all the antifungals, although the amount of released drugs was different. The sustained release of polyene antifungals from fiber mats indicated significant drug–gelatin interactions.38 At the end of 3 days, the amount of amphotericin B and natamycin released in the medium was 9.5 μg/mL and 8.5 mg/mL, respectively. The amount of terbinafine released was 7.3 μg/mL. Of all the antifungals, fluconazole was released in maximum amounts (14 μg/mL). To understand the loss of activity for other antifungals when incorporated into the gelatin matrix, the MIC of all the antifungals alone against five different C. albicans strains was determined. Table 1 compares the determined MIC of various antifungal agents. Amphotericin B displayed the lowest MIC followed by natamycin against all the C. albicans strains examined. Interestingly, four C. albicans strains showed resistance to fluconazole as the MIC was >64 μg/mL. A good correlation was observed between the amounts of antifungals released and MIC values of free antifungals against particular strains of C. albicans. Thus, poor antifungal properties and release characteristics are responsible for apparent loss of activity of azoles and terbinafine upon incorporation into the gelatin matrix.


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)

Cumulative release profile of antifungals form gelatin fiber mats.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ijn-9-2439: Cumulative release profile of antifungals form gelatin fiber mats.
Mentions: The cumulative release profile for various antifungals was determined by UV spectrophotometry (Figure 5). The amount of antifungals released is expressed as μg/mg of fiber mats. The release profile was similar for all the antifungals, although the amount of released drugs was different. The sustained release of polyene antifungals from fiber mats indicated significant drug–gelatin interactions.38 At the end of 3 days, the amount of amphotericin B and natamycin released in the medium was 9.5 μg/mL and 8.5 mg/mL, respectively. The amount of terbinafine released was 7.3 μg/mL. Of all the antifungals, fluconazole was released in maximum amounts (14 μg/mL). To understand the loss of activity for other antifungals when incorporated into the gelatin matrix, the MIC of all the antifungals alone against five different C. albicans strains was determined. Table 1 compares the determined MIC of various antifungal agents. Amphotericin B displayed the lowest MIC followed by natamycin against all the C. albicans strains examined. Interestingly, four C. albicans strains showed resistance to fluconazole as the MIC was >64 μg/mL. A good correlation was observed between the amounts of antifungals released and MIC values of free antifungals against particular strains of C. albicans. Thus, poor antifungal properties and release characteristics are responsible for apparent loss of activity of azoles and terbinafine upon incorporation into the gelatin matrix.

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