Redox-responsive and mucoadhesive nanoparticles: An overlooked synergy in modern drug delivery

The continuous advancement of therapeutic technologies has intensified the pursuit of drug delivery systems that respond intelligently to physiological and pathological stimuli, thereby enabling precise, localized, and sustained therapeutic outcomes. Among redox-based approaches, systems responsive to intracellular glutathione (GSH) have attracted particular attention due to their ability to trigger disulfide bond cleavage and controlled release within diseased tissues. Mucoadhesive systems, on the other hand, prolong residence time on mucosal surfaces through non-covalent interactions and covalent bond formation, thereby facilitating increased absorption and decreased clearance. Despite their individual successes, the integration of these two mechanisms remains underexplored. This review critically examines the coupling of redox sensitivity and mucoadhesion, highlighting how disulfide-based bonds can simultaneously function as both redox-cleavable and mucoadhesive moieties.