Thermogels: In Situ Gelling Biomaterial

Abstract

In situ gel delivery systems are preferred over conventional systems due to sustained and prolonged release action of therapeutic payload onto the targeted site. Thermogel, a form of in situ gel-forming polymeric formulation, undergoes sol-gel transition after administration into the body. At room temperature, the system is an aqueous polymer solution that easily entraps therapeutic payload by mixing. Upon injection, the higher physiological temperature causes gelation in situ because of the presence of thermosensitive polymers. The gel degrades gradually over time, allowing sustained release of therapeutics localized to the site of interest. This minimizes systemic toxicity and improved efficacy of drug release to the targeted site. Thermogel properties can be easily altered for specific applications via substitution and modification of components in diblock and triblock copolymer systems. The feasibility of fine-tuning allows modifications to biodegradability, biocompatibility, biological functionalization, mechanical properties, and drug release profile. This review summarized recent development in thermogel research with a focus on synthesis and self-assembly mechanisms, gel biodegradability, and applications for drug delivery, cell encapsulation and tissue engineering. This review also assessed inadequacy of material properties as a stand-alone factor on therapeutic action efficacy in human trials, with a focus on OncoGel, an experimental thermogel that demonstrated excellent individual or synergistic drug delivery system in preclinical trials but lacked therapeutic impact in human trials. Detailed analysis from all aspects must be considered during technology development for a successful thermogel platform in drug delivery and tissue engineering.

Keywords: LCST; injectable hydrogels; sol−gel transition; thermosensitive polymers.