pH-responsive delivery of azelaic acid from citric acid-crosslinked hydroxypropyl methylcellulose/poly(vinyl alcohol) nanofibers

Fabricating stable, functional nanofibers from hydroxypropyl methylcellulose (HPMC) remains a significant challenge due to its poor electrospinnability and high water-solubility. This work overcomes these limitations by engineering a novel, pH-responsive platform via electrospinning HPMC with poly(vinyl alcohol) (PVA) and applying a safe, green thermal crosslinking with citric acid. This strategy converted the polymer blend from a rapidly dissolving mat into a robust, smart system. Characterization (SEM, FTIR, DSC) confirmed uniform, bead-free morphology, successful ester-bond formation, and enhanced thermal stability. Crosslinking induced a super-hydrophilic surface (WCA 16.3°), favorable for biological fluid interaction. The platform's function was demonstrated with azelaic acid (AzA), where crosslinking transformed its release profile from a rapid burst (>90% in 2 h) to a finely tuned, pH-dependent mechanism. The crosslinked mats provided a smart, sustained release: minimal at pH 4.5 (healthy skin), moderate at pH 6.0, and maximum at pH 7.4 (diseased skin), achieving over 87% release. Kinetic modeling (Korsmeyer-Peppas model) confirmed that drug transport is governed by Fickian diffusion, with the rate profoundly accelerated by pH-triggered swelling. This study establishes a scalable, biocompatible, and intelligent nanofibrous drug delivery platform for on-demand dermatological therapies and advanced wound dressings.