Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease.

Uveitis is a complex ocular inflammatory disease with a multifactorial etiology that can result in blindness. Although corticosteroid eye drops are the primary treatment for anterior uveitis, their efficacy is limited by low bioavailability, adverse effects, and a narrow focus on inflammation. In this study, the multifunctional hydrogel eye drops (designated as DCFH) were developed by incorporating the anti-inflammatory agent dexamethasone (DSP) and reactive oxygen species (ROS) scavenger cerium-based metal-organic frameworks (Ce-MOFs) into thermosensitive triblock copolymer F127 for the synergistic treatment against uveitis. The resulting F127 eye drops offer a favorable alternative to ophthalmic solution due to its thermosensitivity, thixotropy, light transmittance, improved ocular bioavailability, and unexpected anti-inflammatory efficacy. Notably, the participation of nanoporous Ce-MOFs, functional drug carriers, not only reduces ROS level but also boosts the anti-inflammatory activity of DSP in vitro. Therapeutically, the multifunctional DCFH exhibits superior efficacy in treating endotoxin-induced uveitis by mitigating the ophthalmic inflammatory reaction, suppressing inflammatory cytokines (e.g., TNF-α, IL-6, and IL-17) and downregulating the expression of iNOS and NLPR3. This synergistic treatment provides a valuable and promising approach for the management of uveitis and other ocular inflammatory conditions.

Engineering Hibiscus-Like Riboflavin/ZIF-8 Microsphere Composites to Enhance Transepithelial Corneal Cross-Linking.

Riboflavin-5-phosphate (RF) is the most commonly used photosensitizer in corneal cross-linking (CXL), but its hydrophilicity and negative charge limit its penetration through the corneal epithelium into the stroma. To enhance the corneal permeability of RF and promote its efficacy in the treatment of keratoconus, novel hibiscus-like RF@ZIF-8 microsphere composites [6RF@ZIF-8 NF (nanoflake)] are prepared using ZIF-8 nanomaterials as carriers, which are characterized by their hydrophobicity, positive potential, biocompatibility, high loading capacities, and large surface areas. Both hematoxylin and eosin endothelial staining and TUNEL assays demonstrate excellent biocompatibility of 6RF@ZIF-8 NF. In in vivo studies, the 6RF@ZIF-8 NF displayed excellent corneal permeation, and outstanding transepithelial CXL (TE-CXL) efficacy, slightly better than the conventional CXL protocol. Furthermore, the special hibiscus-like structures of 6RF@ZIF-8 NF meant that it has better TE-CXL efficacy than that of 6RF@ZIF-8 NP (nanoparticles) due to the larger contact area with the epithelium and the shorter RF release passage. These results suggest that the 6RF@ZIF-8 NF are promising for transepithelial corneal cross-linking, avoiding the need for epithelial debridement.

Hydrogel eye drops as a non-invasive drug carrier for topical enhanced Adalimumab permeation and highly efficient uveitis treatment.

Uveitis is one of the most popular blind-causing eye diseases worldwide. Adalimumab (ADA) is used for the uveitis treatment through systemic or intravitreal injection at the expense of systemic side effects and increased medical risks. Although eye drops, a non-invasive topical treatment, could be a potential strategy to reduce side effects, it remains challenging to apply due to limited bioavailability mainly linked to poor retention time and permeation capacity for eye biological barriers. Here, we reported hydrogel eye drops composed of low-deacetylated chitosan and ß-glycerophosphate as an ADA carrier and tested its toxicity, tolerability, intraocular permeability, and efficacy of non-invasive treatment for uveitis. It's found the ADA-loaded hydrogel eye drops were more efficient than free ADA both in permeation rate and clinical efficacy for uveitis, Overall, this study provides a friendly non-invasive strategy to improve drug permeation rate and uveitis treatment efficacy, which may be valuable to clinically ophthalmic medication.