Abstract

MUCOADHESIVE DRUG DELIVERY SYSTEMS: MECHANISTIC FOUNDATIONS, ADVANCED POLYMERS, PHARMACEUTICAL APPLICATIONS, AND TRANSLATIONAL PERSPECTIVES

*Mr. Yash Kishor Gangurde, Ms. Prachiti Sanjay Jagtap, Mrs. Smita Rajendra Rupvate

Abstract

The therapeutic efficacy of conventional drug delivery systems is frequently compromised by rapid mucociliary clearance, enzymatic degradation, and short residence times at biological absorption sites. Mucoadhesive drug delivery systems (MDDS) have emerged as a robust pharmaceutical strategy to overcome these physiological hurdles by utilizing the interfacial forces between polymeric carriers and mucosal membranes. This review critically examines the biophysical and molecular basis of mucoadhesion, with a particular focus on the transition from classical theories—such as wetting, diffusion, and adsorption—to advanced covalent bonding mechanisms facilitated by second-generation polymers. The evolution of mucoadhesive materials, ranging from natural polysaccharides (chitosan, alginate) to sophisticated thiolated, catechol-functionalized, and stimuli-responsive smart hydrogels. A route-specific synthesis is provided for route-wise applications, including buccal, nasal, ocular, gastrointestinal, and vaginal delivery, highlighting the impact of MDDS on bypassing first-pass metabolism and enhancing drug bioavailability. Particular emphasis is placed on recent technological innovations (2020–2026), including 3D-printed mucoadhesive platforms and nanotechnology-driven strategies that balance mucoadhesion with mucus penetration. Finally, we address the current translational challenges, including the lack of standardized characterization methods and regulatory hurdles, and outline future perspectives for personalized mucosal therapy. Collectively, the evidence is synthesized to identify design principles, translational barriers, and research priorities for the next generation of localized and systemic transmucosal delivery systems.

Keywords: Mucoadhesion; Thiolated polymers; Mucosal drug delivery; Mucin interaction; Bioavailability enhancement; Nanotechnology; Smart hydrogels; Stimuli-responsive systems; 3D printing; Pharmaceutical translation.