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Nystatin\u2019s hydrophobicity, poor bioavailability, and susceptibility to degradation restrict its clinical utility. In this study, electrospun pectin\u2013carboxymethyl cellulose (CMC)\u2013polyvinyl alcohol (PVA) nanofibers loaded with nystatin (Nys-NF) were developed as a pH-responsive antifungal biointerface. The optimization of electrospinning parameters enabled the fabrication of uniform, porous nanofibers with average fiber diameters of 193 \u00b1 16 nm for blank nanofibers (NF2) and 264 \u00b1 25 nm for Nys-NF. Comprehensive physicochemical characterization confirmed effective physical crosslinking between polymers and loading of nystatin with an encapsulation efficiency of 60.6%. Nys-NF demonstrated pH-responsive behavior, where acidic conditions (pH 5.5) promoted protonation-induced deswelling and matrix dissolution, driving enhanced nystatin release. Nys-NF displayed significant antifungal and antibiofilm activity against Candida albicans (CA), Candida glabrata (CG), and Cryptococcus neoformans (CN). Morphological analysis revealed disruption in biofilm architecture and loss of extracellular matrix components. Mechanistic assays indicated depletion in ergosterol and cell surface hydrophobicity. Nys-NF demonstrated considerable antioxidant activity and cytocompatibility with HEK-293 cells. Conclusively, the developed pH-adaptive polyelectrolyte-based nanofibrous matrices represented a promising localized antifungal delivery system for combatting resilient mucosal fungal biofilms.<\/jats:p>","DOI":"10.1021\/acsabm.6c01142","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:09:18Z","timestamp":1788534558000},"page":"8698-8718","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Nystatin-Loaded pH-Responsive Pectin-Carboxymethyl Cellulose-Based Polyelectrolyte Nanofiber Matrices for Antifungal Therapy"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7137-6572","authenticated-orcid":true,"given":"Bhawana","family":"Yadav","sequence":"first","affiliation":[{"name":"Graphic Era Deemed to be University , , , ,","place":["Dehradun, Uttarakhand, India, 248001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishchay","family":"Verma","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Roorkee , , , ,","place":["Roorkee, Uttarakhand, India, 247667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Graphic Era Deemed to be University , , , ,","place":["Dehradun, Uttarakhand, India, 248001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3801-7134","authenticated-orcid":true,"given":"Krishna Mohan","family":"Poluri","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Roorkee , , , ,","place":["Roorkee, Uttarakhand, India, 247667"]},{"name":"Indian Institute of Technology Roorkee , , , ,","place":["Roorkee, Uttarakhand, India, 247667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8556-1752","authenticated-orcid":true,"given":"Payal","family":"Gupta","sequence":"additional","affiliation":[{"name":"Graphic Era Deemed to be University , , , ,","place":["Dehradun, Uttarakhand, India, 248001"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"2","key":"2026092100084298300_cit1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/1040841X.2021.1950121","article-title":"Biofilm Formation in Clinically Relevant Filamentous Fungi: A Therapeutic Challenge","volume":"48","author":"Roudbary","year":"2022","journal-title":"Crit. 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