Polymer-based in-situ gelling nanoplatforms for buccal drug delivery: a comprehensive review of advances and challenges

The buccal route offers a promising alternative for local and systemic drug delivery by utilizing the oral mucosa’s high permeability to bypass first-pass metabolism and enhance bioavailability. However, rapid saliva clearance and continuous oral movements pose challenges to drug retention, often requiring frequent re-dosing. This review highlights the potential of nanocarrier-based in-situ gelling systems that utilize both natural (e.g., gellan gum, chitosan) and synthetic (e.g., poloxamers, PLGA) polymers to enhance mucoadhesion and gel formation. Nanocarriers like polymeric nanoparticles, liposomes, and micelles enhance drug solubility, stability, and targeting. Promising preclinical and clinical results indicate their effectiveness in treating oral diseases and delivering systemic therapies, though challenges in formulation stability, manufacturing, regulatory approval, and clinical validation remain. Addressing these hurdles is essential to fully realize the potential of these systems, making nanocarrier-mediated in-situ gels a versatile approach to improving bioavailability and patient compliance.