Wang Chaoqun, Wu Tong, Li Yidi, Liu Jie, Wang Yanshai, Wang Kefeng, Li Yang, Leng Xuefei
State Key Laboratory of Fine Chemicals, Liaoning Key Laboratory of Polymer Science and Engineering, Department of Polymer Science and Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
SINOPEC Ningbo New Materials Research Institute Company Limited, Ningbo 315000, China.
Polymers (Basel). 2025 Apr 10;17(8):1030. doi: 10.3390/polym17081030.
Amphiphilic block copolymers with complex topologies (e.g., star and brush topologies) have attracted significant attention in drug delivery owing to their superior performance over linear micelles. However, their precise synthesis and structure-property relationships require further investigation. In this study, hydroxylated polybutadiene with adjustable topology and hydroxyl group density was employed as a macroinitiator to synthesize well-defined amphiphilic poly (ethylene oxide)--poly(-caprolactone---valerolactone) (PEO--P(CL--VL)) copolymers via ring-opening polymerization (ROP). A series of linear, star, linear-comb, and star-comb copolymers were prepared as curcumin-loaded micellar carriers for the study. The self-assembly behavior, drug encapsulation efficiency, and in vitro release profiles of these copolymers in aqueous environments were systematically investigated. The results demonstrated that increasing the branch length of star-comb copolymers effectively reduced micelle size from 143 to 96 nm and enhanced drug encapsulation efficiency from 27.3% to 39.8%. Notably, the star-comb architecture exhibited 1.2-fold higher curcumin encapsulation efficiency than the linear counterparts. Furthermore, the optimized star-comb nanoparticles displayed sustained release kinetics (73.38% release over 15 days), outperforming conventional linear micelles. This study establishes a quantitative structure-property relationship between copolymer topology and drug delivery performance, providing a molecular design platform for programmable nanocarriers tailored to diverse therapeutic requirements of various diseases.
具有复杂拓扑结构（如星形和刷形拓扑结构）的两亲性嵌段共聚物由于其相对于线性胶束的优越性能，在药物递送领域引起了广泛关注。然而，它们的精确合成以及结构-性能关系仍需要进一步研究。在本研究中，具有可调节拓扑结构和羟基密度的羟基化聚丁二烯被用作大分子引发剂，通过开环聚合（ROP）合成了定义明确的两亲性聚（环氧乙烷）-聚（-己内酯---戊内酯）（PEO--P(CL--VL)）共聚物。制备了一系列线性、星形、线性-梳形和星形-梳形共聚物作为载姜黄素的胶束载体用于研究。系统地研究了这些共聚物在水性环境中的自组装行为、药物包封效率和体外释放曲线。结果表明，增加星形-梳形共聚物的支链长度可有效将胶束尺寸从143 nm减小至96 nm，并将药物包封效率从27.3%提高至39.8%。值得注意的是，星形-梳形结构的姜黄素包封效率比线性对应物高1.2倍。此外，优化后的星形-梳形纳米颗粒表现出缓释动力学（15天内释放73.38%），优于传统的线性胶束。本研究建立了共聚物拓扑结构与药物递送性能之间的定量结构-性能关系，为针对各种疾病不同治疗需求定制的可编程纳米载体提供了一个分子设计平台。
