A simple method for fabricating drugs containing a cis-o-diol structure into guanosine-based supramolecular hydrogels for drug delivery

Supramolecular hydrogels are attractive biomaterials for local drug delivery owing to their excellent self-healing, injectable, biodegradable, and biocompatible properties. However, traditional drug-loading approaches based on non-covalent encapsulation and covalent bonding have shown problems such as rapid or difficult drug release, complex reaction processes, low reaction efficiency, and decreased drug activity. Therefore, there is a need to find a simple and efficient method to load drugs into hydrogels, which possess stable drug release ability without impairing drug efficacy. In this study, we introduce dynamic borate ester bonds via a simple one-pot method to load cis-o-diol-containing drugs into guanosine (G)-based supramolecular hydrogels. The experimental results confirm that the dynamic covalent borate ester bonds are formed based on the cis-o-diol groups of the drug and the G in these hydrogels. Meanwhile, the as-prepared G-based hydrogels not only possess self-healing properties and injectability but also have satisfactory biodegradability and biocompatibility. Additionally, the drug can be released from the G-based hydrogel according to the pH-responsive cleavage of the borate ester bonds without affecting drug activity. Overall, these results indicate that the simple one-pot method of utilizing the dynamic borate bond can provide a valuable reference for the design of hydrogel dosage forms.