Luo Yan-Ling, Zhang Xue-Yin, Wang Yuan, Han Fang-Jie, Xu Feng, Chen Ya-Shao
Key Laboratory of Macromolecular Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, P. R. China.
J Mater Chem B. 2017 May 7;5(17):3111-3121. doi: 10.1039/c7tb00073a. Epub 2017 Apr 5.
pH-Sensitive H-type multiblock copolymers, namely, poly(methacrylic acid)-block-epoxidized hydroxyl-terminated polybutadiene-block-poly(methacrylic acid) (PMAA-b-epoHTPB-b-PMAA), were synthesized by atom-transfer radical polymerization and subsequent in situ epoxidation by peracetic acid and characterized by H NMR, FT-IR and SEC techniques. The impact of epoxidation on the physicochemical and biomedical properties of copolymer self-assembly micelle nanoparticles was investigated by fluorescence spectrometry, DLS, TEM and an MTT assay. The experimental results indicated that epoxidation resulted in the formation of more stable copolymer micelle nanoparticles with a lower critical micelle concentration, smaller micelle size, and higher loading capacity and encapsulation efficiency of drugs than those without epoxidation. In particular, epoxidized copolymer micelle nanoparticles exhibited reasonable pH sensitivity at a pH of 5.3-5.6. The hydrophobic anticancer drug paclitaxel (PTX) displayed faster release rates from epoxidized nanomicelles than from unepoxidized nanomicelles in a PBS solution of a pH of 4.8-6.6, whereas in PBS of a pH of 7.4 smaller amounts of PTX were released from epoxidized nanomicelles than from unepoxidized nanomicelles. Epoxidized copolymer nanomicelles were reasonably biodegradable after the drug was released, and their degradation rate was faster than that of their unepoxidized counterparts. An MTT assay was performed to determine the biocompatibility of epoxidized copolymer micelle nanoparticles and the anticancer activities of PTX-loaded nanomicelles, which were important for applications in the therapy of cancers as a controlled-release drug carrier.
通过原子转移自由基聚合反应以及随后用过氧乙酸进行原位环氧化反应，合成了pH敏感型H型多嵌段共聚物，即聚（甲基丙烯酸）-嵌段-环氧化羟基封端聚丁二烯-嵌段-聚（甲基丙烯酸）（PMAA-b-epoHTPB-b-PMAA），并采用氢核磁共振（H NMR）、傅里叶变换红外光谱（FT-IR）和尺寸排阻色谱（SEC）技术对其进行了表征。通过荧光光谱法、动态光散射（DLS）、透射电子显微镜（TEM）和MTT法研究了环氧化反应对共聚物自组装胶束纳米颗粒的物理化学和生物医学性质的影响。实验结果表明，与未环氧化的情况相比，环氧化反应导致形成了更稳定的共聚物胶束纳米颗粒，其临界胶束浓度更低、胶束尺寸更小，并且药物的负载量和包封率更高。特别是，环氧化共聚物胶束纳米颗粒在pH值为5.3 - 5.6时表现出合理的pH敏感性。在pH值为4.8 - 6.6的磷酸盐缓冲盐水（PBS）溶液中，疏水性抗癌药物紫杉醇（PTX）从环氧化纳米胶束中的释放速率比从未环氧化纳米胶束中的释放速率更快，而在pH值为7.4的PBS中，从环氧化纳米胶束中释放的PTX量比从未环氧化纳米胶束中释放的量少。药物释放后，环氧化共聚物纳米胶束具有合理的生物降解性，并且其降解速率比未环氧化的对应物更快。进行了MTT法以确定环氧化共聚物胶束纳米颗粒的生物相容性以及负载PTX的纳米胶束的抗癌活性，这对于作为控释药物载体应用于癌症治疗至关重要。
