Engineering Enhanced Interface Attachment for Sustained Ocular Drug Delivery: Mussel Foot Protein Incorporated Pullulan/Gellan Gum Nanofibers

Abstract Effective treatment of ocular inflammation is hindered by limited drug uptake and rapid clearance, resulting in poor bioavailability and frequent dosing of conventional eye drops. To improve drug retention and bioavailability, we designed and manufactured electrospun mucoadhesive nanofibers based on modified mussel foot protein (mMefp-3). Their composition and small diameter (≈250 nm) provide a high surface area, enabling rapid water uptake and in situ gelation on the ocular surface. SEM, light, and fluorescence microscopy confirmed homogeneous, smooth, and bead-free fibers. Ocular residence studies demonstrated prolonged retention and a shift from first-order to zero-order clearance kinetics. In vitro cell culture assays with fibroblasts, and corneal epithelial cells confirmed the biocompatibility of mMefp-3 loaded nanofiber constructs. These findings demonstrate that mMefp-3 incorporation enhances ocular drug residence while maintaining biocompatibility, making these nanofibers a promising ocular drug delivery system.