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

Abstract

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.

A “T.E.S.T.” hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair

“…On one hand, CXL technology using RF is internationally recognized as the main treatment to prevent and delay the progression of keratoconus [ 23 ]. Accordingly, ROS generated during RF photosensitization mediates the production of new covalent bonds between collagen molecules, leading to an increase in biomechanical strength and stiffness of the corneal stroma [ 24 , 25 ]. The Young's modulus of collagen-based hydrogel has been reported to significantly increase after UV irradiation mediated by RF [ [26] , [27] , [28] ].…”

“…Corneal cross-linking (CXL), an FDA-approved procedure for slowing the progression of keratoconus, uses UV-A light and riboflavin-5-phosphate (RF) to induce cross-linking of collagen [ 23 ]. Reactive oxygen species (ROS) generated during RF photosensitization mediates the production of new covalent bonds between collagen molecules, leading to an increase in biomechanical strength and stiffness of the corneal stroma [ 24 , 25 ]. Of note, RF has a high absorption effect on UV (∼370 nm) rays, preventing most UV light from passing through the cornea.…”

Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking

“… 35 However, patients involved in this study were relatively milder cases. A novel hibiscus-like microsphere composite RF@ZIF-8 was developed as a carrier to promote riboflavin into the corneal stroma, 36 which presented a better transepithelial CXL effect especially in avoiding the destruction of the cornea. At present, this composite has not been verified in patients with clinical KC.…”

Hollow Hierarchical Porous and Antihydrolytic Spherical Zeolitic Imidazolate Frameworks for Enzyme Encapsulation and Biocatalysis

“…Three of them, the peak at 132.95, 133.84, and 140.03 eV, respectively, should represent the P 2p 3/2 , P 2p 1/2 , and the Zn 3s or freshly created P−Zn bond, respectively (Figure S3c). 40 The generation of more Zn−O bonds during enzyme loading will improve the structural stability of the hydrolysis of water. 41 Certainly, the high-resolution XPS spectra of Zn 2p showed that the binding energy peaks of each sample were concentrated at 1021.92 (Zn 2p 3/2 ) and 1044.98 eV (Zn 2p 1/2 ) (Figure S3d), which is consistent with the reported Zn-based MOFs, indicating that the different stages of treatment did not cause substantial changes in the structure of ZIF-8.…”