Background: Oral lichen planus (OLP) is a chronic autoimmune disease of the oral mucosa, classified among potentially malignant oral disorders (OPMDs). It is characterized by keratinocyte apoptosis and persistent inflammation. Standard treatments involve topical corticosteroids administered via mouthwashes, gels, or ointments, but these require frequent application, have limited retention, and may cause side effects. To address these limitations, this study aimed to develop an innovative dexamethasone delivery system targeting the oral cavity, based on poly(lactic acid) (PLA) fibers coated with chitosan (CS) and poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Methods: CS-coated PLA fibers were characterized for their mucoadhesive and cytocompatibility properties, while PLGA nanoparticles were analyzed for size, shape, encapsulation efficiency, cellular uptake, drug release efficiency, and cytocompatibility. Results: Both polymers demonstrated cytocompatibility, and chitosan-coated PLA fibers exhibited mucoadhesive properties. PLGA nanoparticles were effectively internalized by the cells and successfully released the drug into the cytoplasm. The combination of CS-coated PLA fibers and PLGA nanoparticles provided dual benefits: mucoadhesion and efficient cellular uptake, even under conditions simulating salivation. Conclusions: These findings highlight the potential of the proposed system to improve mucoadhesive drug delivery. Further optimization is needed to enhance patient compliance and therapeutic efficacy.

Drug delivery systems have revolutionized the clinical field by enabling the targeted, controlled, and sustained release of therapeutic agents, minimizing side effects and maximizing efficacy. Among the various drug delivery platforms, polymer-based systems have gained significant attention due to their versatility and biocompatibility. This study investigates the release of dexamethasone and clobetasol propionate from PLA (poly(lactic acid)) fibers in a cellular culture system. The release profiles were analyzed over 1, 6, and 24 h using high-performance liquid chromatography (HPLC), showing a gradual, continuous release, with clobetasol exhibiting slower release due to its poor water solubility. The presence of fibroblasts did not significantly affect the drug release, and the concentrations increased over time. An intracellular recovery test revealed that both drugs entered the cells, although their concentrations were below the limit of quantification (LOQ). Measurements of the remaining drug in the fibers confirmed a sustained release, with no significant difference between conditions with and without cells. These results highlight the potential of PLA fibrous membranes for controlled drug delivery, though further research is needed to optimize release and improve intracellular quantification for more effective therapeutic applications.