Phenylboronic acid-functionalised gelatin/PVA films for enhanced vaginal mucoadhesion and sustained metronidazole release

This study aimed to develop gelatin films with enhanced mucoadhesive retention and controlled metronidazole (MTZ) release for vaginal drug delivery. Gelatin was functionalised with 4-formylphenylboronic acid (FPBA) via Schiff base formation followed by reductive amination to obtain derivatives with different functionalisation levels (Gel-Bor L, Gel-Bor M and Gel-Bor H). Structural changes in gelatin were confirmed by ¹H NMR and FTIR spectroscopy, while pH-dependent electrophoretic mobility revealed a shift in the isoelectric point towards lower pH values following derivatisation. Films were prepared by solvent casting using PVA as a film-forming excipient and characterised in terms of thickness, surface pH, folding endurance, transparency, thermal stability and puncture resistance. Ex vivo mucoadhesion of NaFl-loaded films was assessed on freshly excised sheep vaginal mucosa using a flow-through wash-off assay in vaginal fluid simulant (VFS, pH 4.0). In vitro MTZ release was evaluated using Franz diffusion cells, while cytocompatibility was assessed in HT-29 cells and MSCs using the CCK-8 assay. Gel-Bor/PVA films were uniform, flexible and compatible with simulated vaginal pH. Compared with PVA-only and gelatin/PVA controls, Gel-Bor/PVA films exhibited markedly improved mucosal retention, with Gel-Bor L/PVA and Gel-Bor M/PVA performing comparably to chitosan. Chemical modification of gelatin also prolonged MTZ release: after 16 h, cumulative release decreased from 73.10% for gelatin/PVA to 66.50%, 60.40% and 51.70% for Gel-Bor L/PVA, Gel-Bor M/PVA and Gel-Bor H/PVA, respectively. No cytotoxic effects were detected under the tested conditions for all Gel-Bor/PVA formulations. Overall, this chemical modification transformed gelatin-based films into mucoadhesive, cytocompatible platforms with sustained MTZ release for vaginal application.