Abstract:The intricate anatomical architecture and complex dynamic physiological barriers of the eye severely restrict the intraocular bioavailability of ophthalmic drugs. The limited absorption efficiency of conventional eye drops (<5%) and the high invasive risks associated with intravitreal injections constitute persistent bottlenecks in ophthalmic therapeutics. However, driven by the convergence of materials science and biomedical engineering, intelligent drug delivery systems (SDDS) based on stimulus-responsive mechanisms offer revolutionary strategies for overcoming these physiological barriers and achieving spatiotemporally controlled drug release. These systems leverage specific recognition and response capabilities toward pathological microenvironments or exogenous physical fields. This article systematically reviews recent advances in this domain, providing an in-depth analysis of the physicochemical mechanisms underlying various stimulus-responsive carriers from the perspectives of polymer phase transition thermodynamics and chemical bond cleavage kinetics. Synthesizing preclinical and clinical research data on major ocular diseases—including glaucoma, age-related macular degeneration (AMD), and intraocular infections—we demonstrate the significant advantages of these intelligent systems. Key benefits highlighted include prolonged ocular surface retention, biomarker-triggered on-demand release, and reduced systemic toxicity. Finally, this review critically analyzes the challenges facing these complex formulations regarding sterile scale-up manufacturing, regulatory approval pathways, and clinical translation, while offering perspectives on future development.
