Sivokhin Alexey, Orekhov Dmitry, Kazantsev Oleg, Otopkova Ksenia, Sivokhina Olga, Chuzhaykin Ilya, Spitsina Ekaterina, Barinov Dmitry
Research Laboratory "New Polymeric Materials", Nizhny Novgorod State Technical University, n.a. R.E. Alekseev, 24 Minin Street, 603155 Nizhny Novgorod, Nizhegorodskaya Oblast, Russia.
V.A. Kargin Research Institute of Chemistry and Technology of Polymers with Pilot Plant, 606000 Dzerzhinsk, Nizhegorodskaya Oblast, Russia.
Polymers (Basel). 2024 Dec 14;16(24):3493. doi: 10.3390/polym16243493.
Anionic thermo- and pH-responsive copolymers were synthesized by photoiniferter reversible addition-fragmentation chain transfer polymerization (PI-RAFT). The thermo-responsive properties were provided by oligo(ethylene glycol)-based macromonomer units containing hydrophilic and hydrophobic moieties. The pH-responsive properties were enabled by the addition of 5-20 mol% of strong (2-acrylamido-2-methylpropanesulfonic) and weak (methacrylic) acids. Upon initiation by visible light at 470 nm and in the absence of radical initiators, yields from the ternary copolymers reached 94% in 2.5 h when the process was carried out in continuous flow mode using 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid as a light-sensitive RAFT agent. The polymers were characterized using size exclusion chromatography, IR and NMR spectroscopy, and differential scanning calorimetry. The copolymers featured a sufficiently high molecular weight (93-146 kDa) consistent with theoretical values and satisfactory dispersities in the range of 1.18-1.45. The pH-responsive properties were studied in deionized water, saline, and buffer solutions. Dramatic differences in LCST behavior were observed in strong and weak acid-based polyelectrolytes. The introduction of sulfonic acid units, even in very small amounts, completely suppressed the LCST transition in deionized water while maintaining it in the saline and buffer solutions, with a negligible LCST dependence on the pH. In contrast, the incorporation of weak methacrylic acid demonstrated a pronounced pH dependence. The peculiarities of micelle formation in aqueous solutions were investigated and critical micelle concentrations and their ability to retain pyrene, a hydrophobic drug model, were determined. It was observed that anionic molecular brushes formed small micelles with aggregation numbers of 1-2 at concentrations in the order of 10 mg/mL. These micelles have a high ability to entrap pyrene, which makes them a promising tool for targeted drug delivery.
通过光引发转移终止剂可逆加成-断裂链转移聚合（PI-RAFT）合成了阴离子型热响应和pH响应共聚物。热响应性能由含有亲水和疏水部分的基于聚乙二醇的大分子单体单元提供。通过添加5-20摩尔%的强酸（2-丙烯酰胺基-2-甲基丙烷磺酸）和弱酸（甲基丙烯酸）实现pH响应性能。在470 nm可见光引发且无自由基引发剂的情况下，当使用4-氰基-4-[(十二烷基硫烷基硫代羰基)硫烷基]戊酸作为光敏感RAFT剂以连续流动模式进行该过程时，三元共聚物的产率在2.5小时内达到94%。使用尺寸排阻色谱、红外光谱和核磁共振光谱以及差示扫描量热法对聚合物进行了表征。共聚物具有足够高的分子量（93-146 kDa），与理论值一致，分散度在1.18-1.45范围内令人满意。在去离子水、盐水和缓冲溶液中研究了pH响应性能。在强酸和弱酸基聚电解质中观察到低临界溶液温度（LCST）行为的显著差异。磺酸单元的引入，即使是非常少量，也完全抑制了去离子水中LCST转变，同时在盐水和缓冲溶液中保持该转变，LCST对pH的依赖性可忽略不计。相比之下，弱甲基丙烯酸的掺入表现出明显的pH依赖性。研究了水溶液中胶束形成的特性，并测定了临界胶束浓度及其保留芘（一种疏水性药物模型）的能力。观察到阴离子分子刷在浓度约为10 mg/mL时形成聚集数为1-2的小胶束。这些胶束具有高包封芘的能力这使其成为靶向药物递送的有前途的工具。
