Thermoresponsive injectable sol-gel depot systems for long-acting antidiabetic drug delivery: a critical analysis of polymer chemistry, rheological engineering, and translational challenges

Type 2 diabetes mellitus (T2DM) is an issue that has risen in prevalence rates globally necessitating new and more complex modes of treatment that surpass the conventional pharmacotherapy. This has been made possible by the development of the thermoresponsive sol-gel depot systems that utilizes the phase transition between amphiphilic block copolymer which is temperature dependent in order to form a in-situ semi-solid reservoir after the drug is subcutaneously injected to allow for sustained release of near zero-order release of a drug over a prolonged period. The review is a critical analysis of the physicochemical fundamentals of the thermoresponsible sol-gel systems such as polymer chemistry, rheological behaviour and polymer-drug interaction that defines therapeutic output. The low critical solution temperature (LCST) behaviour is of particular concern in PEG-PLGA -PEG triblock copolymer, Pluronic systems and in new stimulus sensitive polymers. They are systematically evaluated when used with peptide-based antidiabetic therapeutics such as insulin analogues and GLP-1 receptors agonists. Even some of the more advanced techniques of formulations are covered including nanoparticle constructed depots and glucose powered hydrogels. Such critical questions in translations as burst release, thermomechanical instability, immunogenicity, and regulatory limitations are of heightened interest. It is an integration of polymer science, nanotechnology and pharmaceutical engineering review that provides a mechanistic nature in the rational development of the next-generation long-acting injectable depot systems.