The position of the monomers within the polymer chain and the 3D structure of the polymer affect the thermoresponsive properties.

Thermoreversible polymer hydrogels (TRGs) are physical aqueous networks triggered by temperature that find potential applications in tissue engineering (TE) and drug/gene delivery. When systems with lower critical solution temperature (LCST) behaviour are used, the aqueous solution of polymer is mixed with cells or drugs/genes, depending on the desired application, at room temperature and then injected in vivo to form a hydrogel. This in situ forming hydrogel acts as a matrix for tissue regeneration or controlled and targeted release of the compound. This review focuses on discussing the studies in which synthetic TRGs with LCST behaviour have been applied in vivo in model animals. These studies are categorised depending on the general structure of the polymer, as follows: (i) poloxamers (also known as Pluronics®), (ii) degradable polymers, (iii) poly(N‐isopropylacrylamide), (iv) poly(organophosphazene) and (v) poly(2‐ethyl‐2‐oxazoline). In general, when the system is optimised, TRGs provide sustained and topical release of the drugs, thus minimising the undesired side effects. When applied in the TE field, tissue formation was observed. Interestingly, two polymers have reached clinical trials, namely poloxamer 407 (P407, Pluronic® F127, often combined with P188, F68) and Regel® (the formulation of Regel® with the anticancer agent paclitaxel is known as Oncogel®), indicating the challenges that need to be overcome before successful application in clinics. © 2021 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Thermoresponsive polymers with the appropriate structure form physical networks upon changes in temperature, and they find utility in formulation science, tissue engineering, and drug delivery. Here, we report a cost-effective biocompatible alternative, namely OEGMA300₁₅-b-BuMA₂₆-b-DEGMA₁₃, which forms gels at low concentrations (as low as 2% w/w); OEGMA300, BuMA, and DEGMA stand for oligo(ethylene glycol) methyl ether methacrylate (MM = 300 g mol^–1), n-butyl methacrylate, and di(ethylene glycol) methyl ether methacrylate, respectively. This polymer is investigated in depth and is compared to its commercially available counterpart, Poloxamer P407 (Pluronic F127). To elucidate the differences in their macroscale gelling behavior, we investigate their nanoscale self-assembly by means of small-angle neutron scattering and simultaneously recording their rheological properties. Two different gelation mechanisms are revealed. The triblock copolymer inherently forms elongated micelles, whose length increases by temperature to form worm-like micelles, thus promoting gelation. In contrast, Pluronic F127’s micellization is temperature-driven, and its gelation is attributed to the close packing of the micelles. The gel structure is analyzed through cryogenic scanning and transmission electron microscopy. Ex vivo gelation study upon intracameral injections demonstrates excellent potential for its application to improve drug residence in the eye.

In this study, seven thermoresponsive methacrylate terpolymers with the same molar mass (MM) and composition but various architectures were successfully synthesized using group transfer polymerization (GTP). These terpolymers were based on tri(ethylene glycol) methyl ether methacrylate (TEGMA, A unit), n-butyl methacrylate (BuMA, B unit), and 2-(dimethylamino)ethyl methacrylate (DMAEMA, C unit). Along with the more common ABC, ACB, BAC, and statistical architectures, three diblock terpolymers were also synthesized and investigated for the first time, namely (AB)C, A(BC), and B(AC); where the units in the brackets are randomly copolymerized. Two BC diblock copolymers were also synthesized for comparison. Their hydrodynamic diameters and their effective pK_as were determined by dynamic light scattering (DLS) and hydrogen ion titrations, respectively. The self-assembly behavior of the copolymers was also visualized by transmission electron microscopy (TEM). Both dilute and concentrated aqueous copolymer solutions were extensively studied by visual tests and their cloud points (CP) and gel points were determined. It is proven that the aqueous solution properties of the copolymers, with specific interest in their thermoresponsive properties, are influenced by the architecture, with the ABC and A(BC) ones to show clear sol-gel transition.

Thermoresponsive polymers based on oligo(ethylene glycol) (OEG) methyl ether methacrylate monomers from unimers to micelles to precipitation.