'STIMULI-RESPONSIVE MUCOADHESIVE INTRANASAL IN SITU GELS FOR NOSE-TO-BRAIN DRUG DELIVERY: AN ADVANCED REVIEW ON BRAIN-TARGETING EFFICIENCY AND THERAPEUTIC HORIZONS

comprehensive review systematically evaluates the development, physiological mechanisms, polymer chemistry, and brain-targeting performance of stimuli-responsive Mucoadhesive intranasal in situ gels designed for direct nose-to-brain (N2B) drug administration. Methods: A structured search strategy across PubMed and Scopus databases extracted SOTA peer-reviewed research (2019–2026) focusing on thermoresponsive, ion-activated, and pH-dependent polymer matrices combined with Nano carriers. Analytical screening emphasized absolute pharmacokinetic parameters including brain Area Under the Curve (AUC), Brain-Targeting Efficiency (BTE%), and Drug-Targeting Index (DTI). Results: The findings demonstrate that combining Nanoemulsion, solid lipid nanoparticles (SLNs), or polymeric micelles within a smart Mucoadhesive hydrogel matrix extends the localized retention time within the olfactory region from less than 15 minutes to over 6 hours. This architectural shift significantly mitigates rapid mucociliary clearance (MCC) and bypasses the blood-brain barrier (BBB) via direct olfactory and trigeminal neuronal tracks. Conclusion: Stimuli-responsive nasal in situ gels offer a clinically viable, non-invasive platform for treating complex central nervous system (CNS) disorders, exhibiting up to an 8-fold increase in cerebral bioavailability compared to conventional oral therapeutics.