Synthesis and Characterization of In Situ Chitosan/Cyclodextrin/Catechol Gel for Rapamycin Delivery

Abstract Innovative in situ drug‐releasing hydrogels are emerging as a promising therapeutic strategy for anterior segment ocular diseases, leveraging the unique anatomy of the eye. Rapamycin (RAP) is an effective immunosuppressive agent for organ transplantation; however, high hydrophobicity and low bioavailability have strongly constrained its clinical application. Chitosan (CS) is used as the backbone, and RAP can be loaded through supramolecular host‐guest interactions of cyclodextrin (CD) to obtain chitosan‐conjugated‐(cydodextrin with 3,4‐dihydroxyhrocinnamic acid) and loaded with rapamycin (CCH/RAP) with controlled drug release properties. Here, an in situ drug‐releasing hydrogel prepared by a simple amidation reaction is reported. It is discovered that the prepared conjugated polymers can form hydrogel crosslinked networks through non‐covalent bonds. The design of the in situ hydrogel allows for excellent transparency and suitable pore size, which can ensure that it can be used in ocular applications. Moreover, drug release results show that the introduction of CD effectively delays the initial release of RAP. This pioneering work presents an eco‐friendly method for fabricating hydrogels with superior drug delivery capabilities, which hold significant potential in mitigating immune rejection following corneal transplantation.