Thermosensitive In Situ Gels: Mechanisms, Properties, and Applications in Drug Delivery

Thermosensitive hydrogels are polymeric networks that undergo sol-gel transitions in response to temperature changes, offering advantages such as biocompatibility, tunable gelation, and sustained drug release. This review explores the classification, properties, and applications of thermosensitive hydrogels in drug delivery. These hydrogels are categorized as either positive (upper critical solution temperature, UCST) or negative (lower critical solution temperature, LCST) based on their gelation behavior. Their mechanical properties, adhesion, and drug release mechanisms are influenced by factors such as polymer composition, crosslinking density, and environmental conditions. Thermosensitive hydrogels provide targeted, prolonged release, and are applicable across various administration routes, including transdermal, rectal, and cancer therapy. Novel formulations, such as chitosan/pluronic/β-glycerophosphate (CS/PF/BGP) and poly(alanine)-poly(ethylene glycol)-poly(alanine) (PAla-PEG-PAla), combined with micro/nanocarriers, have demonstrated enhanced retention, controlled burst release, and significant potential for advanced biomedical applications. This review highlights the versatility and promise of thermosensitive hydrogels as intelligent biocompatible materials for drug delivery, and offers insights into their properties, mechanisms, and recent advancements in the field.