Mucoadhesive chitosan/polyvinyl alcohol/zinc oxide composite strips enriched with Plectranthus amboinicus...

This study reports the development of a multifunctional composite film (CPZPA) based on chitosan (CHS) and polyvinyl alcohol (PVA), incorporating zinc oxide nanoparticles (ZnONPs), Plectranthus amboinicus leaf extract (PAE), and Amphotericin B (AmB) for localized antifungal therapy. The formulation utilizes biopolymer matrices and plant-derived bioactive compounds to support controlled drug delivery and improved biocompatibility. In contrast to many conventional AmB delivery systems that employ synthetic surfactants or complex lipid carriers, the proposed platform integrates phytochemicals and inorganic nanoparticles within a semi-interpenetrating polymer network to modulate drug release and enhance functional performance. Structural and morphological analyses using FTIR, XRD, TEM/SAED, and FESEM-EDX mapping confirmed the successful incorporation and uniform dispersion of crystalline ZnONPs within the polymer matrix, along with evidence of interfacial interactions between the components. XPS analysis further indicated the presence of phytochemical constituents from PAE on the film surface. Drug release studies demonstrated sustained AmB release with kinetics best described by a non-Fickian diffusion mechanism (R² > 0.99), suggesting contributions from both diffusion and polymer relaxation processes. The composite film exhibited antifungal activity against Candida albicans, Aspergillus flavus, and Aspergillus niger, indicating the potential of the integrated system to enhance antifungal performance compared with individual components. AFM analysis revealed reduced biofilm formation and a smoother surface morphology following treatment. The film exhibited antioxidant, antidiabetic, and anti-inflammatory activities in the evaluated assays. LC-MS/MS and HPLC analysis confirmed the presence of phenolic and flavonoid compounds derived from Plectranthus amboinicus, which might contribute to the observed biological responses. Biodegradation, cytocompatibility, and hemocompatibility evaluations demonstrated favourable safety characteristics, including slower degradation behavior and significantly reduced hemolysis compared with free AmB. Moderate mucoadhesive properties (63.6%) further support prolonged retention at the application site. Overall, the developed CPZPA film represents a promising polymer-nanoparticle composite platform for localized antifungal therapy with controlled drug release and multifunctional biological activity.