Agarwal Anshu, Bobay Benjamin G, Becker Matthew L
Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina 27708, United States.
Department of Radiology, Duke University, Durham, North Carolina 27708, United States.
J Am Chem Soc. 2025 Mar 19;147(11):9386-9395. doi: 10.1021/jacs.4c16415. Epub 2025 Mar 7.
Stimuli-responsive drug delivery systems have expanded the diversity of potential cargos by protecting payloads, extending circulation, and controlling payload release. However, quantitative characterization methods that accurately describe these complex systems are needed to accelerate their translation to the clinic. To this extent, degradable, thermoresponsive polyesters were developed through the ring-opening copolymerization of maleic anhydride and an oligo(ethylene glycol)-functionalized epoxide. The resulting polymers possess a lower critical solution temperature such that they are soluble in aqueous solutions at low temperatures (4-7 °C) but assemble into particles above room temperature (25 °C). The particle size and morphology were tunable through the selection of polymer initiator, forming nanoparticle (ca. 162 nm) and microparticle (ca. 1.85 μm) assemblies using macromolecular polyethylene glycol and small molecule propargyl alcohol initiators, respectively. Diffusion-ordered NMR spectroscopy (DOSY) was used over a range of temperatures to develop molecular weight calibrations using certified poly(ethylene glycol) standards. DOSY was able to monitor the dynamic self-assembly behavior of the thermoresponsive polymers in aqueous solutions, and through distinct diffusion constant shifts, quantify the aggregation number of particle intermediates within the nano- and microparticles.
刺激响应性药物递送系统通过保护有效载荷、延长循环时间和控制有效载荷释放，扩展了潜在药物的多样性。然而，需要准确描述这些复杂系统的定量表征方法，以加速其向临床的转化。在此背景下，通过马来酸酐与低聚（乙二醇）官能化环氧化物的开环共聚反应，合成了可降解的热响应性聚酯。所得聚合物具有较低的临界溶解温度，使其在低温（4 - 7°C）下可溶于水溶液，但在室温（25°C）以上会组装成颗粒。通过选择聚合物引发剂可调节颗粒大小和形态，分别使用大分子聚乙二醇和小分子炔丙醇引发剂，形成纳米颗粒（约162 nm）和微粒（约1.85μm）聚集体。在一系列温度范围内，使用认证的聚（乙二醇）标准品，通过扩散排序核磁共振光谱（DOSY）进行分子量校准。DOSY能够监测热响应性聚合物在水溶液中的动态自组装行为，并通过明显的扩散常数变化，量化纳米颗粒和微粒中颗粒中间体的聚集数。
