Targeting the Oral Mucosa: Emerging Drug Delivery Platforms and the Therapeutic Potential of Glycosaminoglycans.

Research into oral mucosa-targeted drug delivery systems (DDS) is rapidly evolving, with growing emphasis on enhancing bioavailability and precision targeting while overcoming the unique anatomical and physiological barriers of the oral environment. Despite considerable progress, challenges such as enzymatic degradation, limited mucosal penetration, and solubility issues continue to hinder therapeutic success. Recent advancements have focused on innovative formulation strategies-including nanoparticulate and biomimetic systems-to improve delivery efficiency and systemic absorption. Simultaneously, smart and stimuli-responsive materials are emerging, offering dynamic, environment-sensitive drug release profiles. One particularly promising area involves the application of glycosaminoglycans, a class of naturally derived polysaccharides with excellent biocompatibility, mucoadhesive properties, and hydrogel-forming capacity. These materials not only enhance drug residence time at the mucosal site but also enable controlled release kinetics, thereby improving therapeutic outcomes. However, critical research gaps remain: standardized, clinically meaningful mucoadhesion/permeation assays and robust in vitro-in vivo correlations are still lacking; long-term stability, batch consistency of GAGs, and clear regulatory classification (drug, device, or combination) continue to impede scale-up and translation. Patient-centric performance-palatability, mouthfeel, discreet wearability-and head-to-head trials versus standard care also require systematic evaluation to guide adoption. Overall, converging advances in GAG-based films, hydrogels, and nanoengineered carriers position oral mucosal delivery as a realistic near-term option for precision local and selected systemic therapies-provided the field resolves standardization, stability, regulatory, and usability hurdles.