MMP-2/Temperature Dual-Responsive Smart Eutectogels With Strong Tissue Adhesion, Superior Stability, and Adaptability for Glaucoma Treatment

Traditional hydrogel-based drug delivery systems face critical limitations, including poor toughness and adhesion, and low drug utilization efficiency, which collectively limit their efficacy in glaucoma treatment. Deep eutectic solvents (DESs) can effectively address these limitations because they are structurally tunable and exhibit high rates of drug dissolution. Herein, we apply β-cyclodextrin and phytic acid to prepare a novel DES, which was used to fabricate a deep eutectic smart gel drug delivery system (DSGS). The DES establish multi-hydrogen-bonded shielding networks with polymer chains, endowing the DSGS with an ocular tissue-matched modulus and a high toughness of 5.94 MJ·m⁻³. Notably, the DSGS enables precise drug release in response to dual stimuli: matrix metalloproteinase-2 and temperature. We employ 4D printing technology to engineer a novel glaucoma drainage device (GDD) from the DSGS loaded with an antifibrotic drug for glaucoma treatment. Based on the synergistic effect of DSGS and the drug, the GDD regulates intraocular pressure (IOP), suppresses fibrosis, and restructures the extracellular matrix collagen architecture in vivo. Furthermore, the DSGS is injectable and exhibits strong tissue adhesion. Following minimally invasive implantation into the conjunctiva, a stable IOP was maintained for 30 days. This innovative design represents a promising direction for future drug delivery.