Constantinou Anna P, Nele Valeria, Doutch James J, S Correia Joana, Moiseev Roman V, Cihova Martina, Gaboriau David C A, Krell Jonathan, Khutoryanskiy Vitaliy V, Stevens Molly M, Georgiou Theoni K
Department of Materials, Imperial College London, London SW7 2AZ, UK.
Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
Macromolecules. 2022 Mar 8;55(5):1783-1799. doi: 10.1021/acs.macromol.1c02123. Epub 2022 Feb 14.
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 OEGMA300--BuMA--DEGMA, 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), -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.
具有适当结构的热响应性聚合物在温度变化时形成物理网络，它们在制剂科学、组织工程和药物递送中具有实用价值。在此，我们报告一种具有成本效益的生物相容性替代品，即OEGMA300 - BuMA - DEGMA，它在低浓度（低至2% w/w）时形成凝胶；OEGMA300、BuMA和DEGMA分别代表聚（乙二醇）甲基醚甲基丙烯酸酯（MM = 300 g/mol）、甲基丙烯酸丁酯和二（乙二醇）甲基醚甲基丙烯酸酯。对这种聚合物进行了深入研究，并将其与市售同类产品泊洛沙姆P407（普朗尼克F127）进行了比较。为了阐明它们在宏观尺度上的凝胶化行为差异，我们通过小角中子散射研究它们的纳米尺度自组装，并同时记录它们的流变学性质。揭示了两种不同的凝胶化机制。三嵌段共聚物固有地形成细长的胶束，其长度随温度增加形成蠕虫状胶束，从而促进凝胶化。相比之下，普朗尼克F127的胶束化是由温度驱动的，其凝胶化归因于胶束的紧密堆积。通过低温扫描和透射电子显微镜分析凝胶结构。前房内注射后的离体凝胶化研究表明其在改善药物在眼内滞留方面具有极好的应用潜力。
