Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

Rajamani Lakshminarayanan,1,2 Radhakrishnan Sridhar,3,4 Xian Jun Loh,5 Muruganantham Nandhakumar,1 Veluchamy Amutha Barathi,1,6 Madhaiyan Kalaipriya,3,4 Jia Lin Kwan,1 Shou Ping Liu,1,2 Roger Wilmer Beuerman,1,2 Seeram Ramakrishna3,4,7 1Singapore Eye Research Institute, 2Signature Research Program...

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Autores principales: Lakshminarayanan R, Sridhar R, Loh XJ, Nandhakumar M, Barathi VA, Kalaipriya M, Kwan JL, Liu SP, Beuerman RW, Ramakrishna S
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:be3a9f87322248b7ba5a939e379eb4942021-12-02T02:10:25ZInteraction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats1178-2013https://doaj.org/article/be3a9f87322248b7ba5a939e379eb4942014-05-01T00:00:00Zhttp://www.dovepress.com/interaction-of-gelatin-with-polyenes-modulates-antifungal-activity-and-a16884https://doaj.org/toc/1178-2013 Rajamani Lakshminarayanan,1,2 Radhakrishnan Sridhar,3,4 Xian Jun Loh,5 Muruganantham Nandhakumar,1 Veluchamy Amutha Barathi,1,6 Madhaiyan Kalaipriya,3,4 Jia Lin Kwan,1 Shou Ping Liu,1,2 Roger Wilmer Beuerman,1,2 Seeram Ramakrishna3,4,7 1Singapore Eye Research Institute, 2Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, 3Department of Mechanical Engineering, National University of Singapore, 4Center for Nanofibers and Nanotechnology, National University of Singapore, 5Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 3 Research Link, Singapore, 6Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 7NUS Nanoscience and Nanotechnology Initiative, 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. Keywords: fungal infections, electrospinning, antifungals, controlled release, drug–matrix interactionsLakshminarayanan RSridhar RLoh XJNandhakumar MBarathi VAKalaipriya MKwan JLLiu SPBeuerman RWRamakrishna SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2439-2458 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Lakshminarayanan R
Sridhar R
Loh XJ
Nandhakumar M
Barathi VA
Kalaipriya M
Kwan JL
Liu SP
Beuerman RW
Ramakrishna S
Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats
description Rajamani Lakshminarayanan,1,2 Radhakrishnan Sridhar,3,4 Xian Jun Loh,5 Muruganantham Nandhakumar,1 Veluchamy Amutha Barathi,1,6 Madhaiyan Kalaipriya,3,4 Jia Lin Kwan,1 Shou Ping Liu,1,2 Roger Wilmer Beuerman,1,2 Seeram Ramakrishna3,4,7 1Singapore Eye Research Institute, 2Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, 3Department of Mechanical Engineering, National University of Singapore, 4Center for Nanofibers and Nanotechnology, National University of Singapore, 5Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 3 Research Link, Singapore, 6Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 7NUS Nanoscience and Nanotechnology Initiative, 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. Keywords: fungal infections, electrospinning, antifungals, controlled release, drug–matrix interactions
format article
author Lakshminarayanan R
Sridhar R
Loh XJ
Nandhakumar M
Barathi VA
Kalaipriya M
Kwan JL
Liu SP
Beuerman RW
Ramakrishna S
author_facet Lakshminarayanan R
Sridhar R
Loh XJ
Nandhakumar M
Barathi VA
Kalaipriya M
Kwan JL
Liu SP
Beuerman RW
Ramakrishna S
author_sort Lakshminarayanan R
title Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats
title_short Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats
title_full Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats
title_fullStr Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats
title_full_unstemmed Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats
title_sort interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/be3a9f87322248b7ba5a939e379eb494
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