Polymer Matrices for Reversible Thermogelling Hydrogels: Principles, Fabrication, and Drug Delivery Prospects

This review presents a comprehensive analysis of modern thermosensitive polymer systems for in situ systems (ISSs) which are used for targeted drug delivery in situ. The main classes of polymers used to create "smart" hydrogels that undergo a "sol-gel" phase transition in response to a temperature stimulus in the physiological range are considered. Key representatives of thermosensitive matrices are described in detail: synthetic block copolymers (poloxamers, block copolymers of polylactic-co-polyglycolic acid with polyethyleneglycol, etc.) and natural, modified natural, and semi-synthetic polymers (chitosan, including in combination with β-glycerophosphate, xyloglucan, etc.). This paper systematizes the advantages and disadvantages of various thermosensitive systems and highlights the key risks in their pharmaceutical development, including the influence of the nature and concentration of the active pharmaceutical ingredients and excipients on the rheological properties and phase transition temperature. Particular attention is paid to the difference between thermoreversible and irreversible gel-forming systems. Modern in vitro, ex vivo, and in vivo methods for evaluating critical quality parameters of thermosensitive systems, such as gelation temperature and time, gel strength, mucoadhesive properties, and release kinetics, are discussed. The need to develop standardized and biologically relevant methods to improve the reproducibility and success of preclinical studies is emphasized. The review is intended to help researchers to make informed choices about polymer matrices and optimize compositions for successful pharmaceutical development.