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 highly invasive nature of intravitreal injections remain persistent bottlenecks in ophthalmic therapeutics. Driven by the convergence of materials science and biomedical engineering, intelligent stimuli-responsive drug delivery systems offer revolutionary strategies to overcome these physiological barriers and achieve spatiotemporally controlled drug release. These systems leverage specific recognition and response capabilities targeted at 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 stimuli-responsive carriers from the perspectives of polymer phase transition thermodynamics and chemical bond cleavage kinetics. By synthesizing preclinical and clinical research data on major ocular diseases, including glaucoma, age-related macular degeneration, and intraocular infections, the significant advantages of these intelligent systems were demonstrated. Highlighted benefits include prolonged ocular surface retention, biomarker-triggered on-demand release, and minimized systemic toxicity. Finally, this review critically analyzes the challenges of translating these complex formulations to the clinic, specifically regarding sterile scale-up manufacturing and regulatory approval pathways, while providing perspectives on future development.
