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.

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

“…The initially translucent sol at 20 °C turned into a turbid gel at 37 °C. The micellar nature of the PEG–PCL–PEG and changes in transparency of the sol and gel states suggest that the sol–to–gel transition of the aqueous PEG–PCL–PEG solutions is a result of aggregation of the micelles (Figure d) . The scanning electron microscopy image of the gel quenched from 37 °C shows the microporous structure of the gel.…”

Advances in drug delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers

“…This response of the hydrogels is mainly governed and tuned by the hydrogel composition, the cross-linking type (chemical or physical) and the degree of cross-linking. There are numerous applications of hydrogels including in particular vehicles for drug delivery, scaffolds for tissue engineering, actuators for optics and fluidics, and model extracellular matrices for biological studies [184][185][186][187][188][189][190]. However, PHB-based hydrogels used as DDS remain quite rare in comparison to the PHB-based nanoparticles, micelles or microparticles.…”

Biodegradable Thermogelling Polymers

“…After gelation, release of the drug by surface erosion is the preferred mechanism because the release profile is smooth. Surface erosion is prevalent in thermogels with highly hydrophobic groups, such as PEG–PHB–PEG and PEG–PCL–PEG thermogels …”