Glycol chitosan thermogels: a versatile platform for advanced drug delivery

Injectable thermogels are promising localized drug delivery platforms as their temperature-triggered in situ gelation facilitates practical administration. However, conventional systems suffer from high critical gelation concentrations, limited biodegradability, cytotoxicity, or acidic degradation, which can cause local inflammation. Glycol chitosan (GC)-based thermogels have emerged as a promising alternative, combining aqueous solubility at physiological pH, biodegradability, biocompatibility, mucoadhesion, low-concentration gelation, and structural versatility.

This review comprehensively examines GC-based thermogels, highlighting how hydrophobic modifications govern their structure-property relationships and thermo-responsive gelation. It evaluates their performance as localized reservoirs for small-molecule drugs, biomacromolecules, and genes across challenging anatomical sites with rapid physiological clearance, including ocular, inner ear, and vaginal sites, while summarizing emerging biofunctional applications in cell delivery, wound healing, and 3D biofabrication. Recent advances in prodrug thermogels, dual crosslinked networks, and biohybrid formulations are also discussed.

To advance GC-based thermogels toward clinical implementation, formulation design must prioritize controlled degradation synchronized with payload release and therapeutic duration. Translation will require standardized polymer characterization, reproducible and scalable manufacturing, sterilization-compatible processing, long-term local safety assessment, and rigorous benchmarking in clinically relevant models. Ultimately, indication-specific formulations with functionality tailored to defined therapeutic needs are more likely to achieve clinical translation than a universal platform approach.