title: Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats.
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.
authors.affiliation: Singapore Eye Research Institute, Singapore ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Rajamani
authors.initials: R
authors.lastname: Lakshminarayanan
authors.affiliation: Department of Mechanical Engineering, National University of Singapore, Singapore ; Center for Nanofibers and Nanotechnology, National University of Singapore, Singapore.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Sridhar
authors.affiliation: Institute of Materials Research and Engineering, ASTAR (Agency for Science, Technology and Research), 3 Research Link, Singapore.
authors.forename: Xian Jun
authors.initials: XJ
authors.lastname: Loh
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Muruganantham
authors.initials: M
authors.lastname: Nandhakumar
authors.affiliation: Singapore Eye Research Institute, Singapore ; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Veluchamy Amutha
authors.initials: VA
authors.lastname: Barathi
authors.affiliation: Department of Mechanical Engineering, National University of Singapore, Singapore ; Center for Nanofibers and Nanotechnology, National University of Singapore, Singapore.
authors.forename: Madhaiyan
authors.initials: M
authors.lastname: Kalaipriya
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Jia Lin
authors.initials: JL
authors.lastname: Kwan
authors.affiliation: Singapore Eye Research Institute, Singapore ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Shou Ping
authors.initials: SP
authors.lastname: Liu
authors.affiliation: Singapore Eye Research Institute, Singapore ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Roger Wilmer
authors.initials: RW
authors.lastname: Beuerman
authors.affiliation: Department of Mechanical Engineering, National University of Singapore, Singapore ; Center for Nanofibers and Nanotechnology, National University of Singapore, Singapore ; NUS Nanoscience and Nanotechnology Initiative, Singapore.
authors.forename: Seeram
authors.initials: S
authors.lastname: Ramakrishna
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry*; D001672:Biocompatible Materials; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D004357:Drug Synergism; D004595:Electroplating / Q000379:methods; D005658:Fungi / Q000187:drug effects / Q000502:physiology*; D005780:Gelatin / Q000737:chemistry*; D008567:Membranes, Artificial; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D012399:Rotation
chemical_list: D000935:Antifungal Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D053769:Nanocapsules; D005780:Gelatin
keywords: antifungals; controlled release; drug–matrix interactions; electrospinning; fungal infections