Smart Stimuli-Responsive Injectable Hydrogels for Precision Drug Delivery: Design, Mechanisms, and Emerging Applications

Abstract

Smart stimuli-responsive injectable hydrogels are new generation of drug delivery systems that promise to revolutionize the field of drug delivery by combining the benefits of minimally invasive drug delivery systems with spatial and temporal control over drug release. This report aims to summarize the recent advances in the design of stimuli-responsive injectable hydrogels, including the polymer backbone, such as polysaccharide-derived hyaluronic acid, and synthetic poly(NIPAM), poly(PEG), and poly(zwitterionic)s, as well as the various cross-linking chemistries, including Schiff base, Michael addition, and physical cross-linking, that enable the design of injectable hydrogels that undergo a solution-to-gel transition in situ in response to various stimuli, such as pH, redox, enzymes, light, ultrasound, and temperature, among others. This review aims to provide a comprehensive summary of the current advances, mechanisms, and perspectives of smart stimuli-responsive injectable hydrogels, including their applications in oncology, ophthalmology, and neurology, as well as their successful outcomes in completely curing tumours, 75% tumour regression using a GSH-responsive peptide gel, and significant functional repair in spinal cord injury repairs using microenvironment-responsive matrices, among many other applications of injectable hydrogels in drug delivery systems. The translation of injectable hydrogels into the clinic, however, is currently hampered by the difficulties in long-term biocompatibility profiling, large-scale sterile production, and regulatory hurdles associated with combination drug products