Advances in mucoadhesive drug delivery systems: Mechanistic insights, pharmacological performance, and translational...

Mucoadhesive drug delivery systems (MDDS) have emerged as an important strategy in modern pharmacology to enhance drug residence time, improve mucosal absorption, and optimize therapeutic performance across diverse administration routes. By enabling intimate and prolonged interactions with mucosal tissues, MDDS directly influence pharmacokinetic and pharmacodynamic outcomes while supporting patient-centric, non-invasive drug delivery. Recent advances in polymer engineering, surface functionalization, and formulation design have further expanded the capability of MDDS to overcome biological barriers and address key limitations associated with conventional dosage forms. This review provides a comprehensive and mechanistically driven analysis of MDDS, focusing on the fundamental principles of mucoadhesion and the physicochemical and biological factors governing adhesive strength, mucus penetration, and controlled drug release. A wide range of mucoadhesive delivery platforms, including films, gels, tablets, patches, hydrogels, and particulate systems, are discussed in relation to their structure-property-function relationships and pharmacological performance across oral, nasal, ocular, gastrointestinal, vaginal, rectal, and pulmonary routes. The role of natural, semi-synthetic, and synthetic polymers, together with advanced functionalization strategies such as thiolation, ligand incorporation, stimuli-responsive networks, and nanotechnology integration, is critically evaluated with respect to enhancing adhesion, permeability, and therapeutic efficacy. Beyond formulation design, the review emphasizes translational and drug discovery-relevant considerations, including Quality by Design (QbD), manufacturing scalability, regulatory and safety expectations, and clinically evaluated and Food and Drug Administration-approved mucoadhesive products. Selected clinical trials and case studies of successful and unsuccessful formulations are examined to highlight key challenges in clinical translation and to identify emerging opportunities. By bridging mechanistic understanding with applied pharmacology and translational development, this review positions MDDS as a versatile and clinically viable platform for advancing next-generation drug delivery strategies and accelerating their progression from discovery to patient care.