Self-assembly hydrogels of therapeutic agents for local drug delivery

Advanced drug delivery systems are of vital importance to enhance therapeutic efficacy. Among various recently developed formulations, self-assembling hydrogels composed of therapeutic agents have shown promising potential for local drug delivery owing to their excellent biocompatibility, high drug-loading efficiency, low systemic toxicity, and sustained drug release behavior. In particular, therapeutic agents self-assembling hydrogels with well-defined nanostructures are beneficial for direct delivery to the target site via injection, not only improving drug availability, but also extending their retention time and promoting cellular uptake. In brief, the self-assembly approach offers better opportunities to improve the precision of pharmaceutical treatment and achieve superior treatment efficacies. In this review, we intend to cover the recent developments in therapeutic agent self-assembling hydrogels. First, the molecular structures, self-assembly mechanisms, and application of self-assembling hydrogels are systematically outlined. Then, we summarize the various self-assembly strategies, including the single therapeutic agent, metal-coordination, enzyme-instruction, and co-assembly of multiple therapeutic agents. Finally, the potential challenges and future perspectives are discussed. We hope that this review will provide useful insights into the design and preparation of therapeutic agent self-assembling hydrogels.