Yang Chufen, Liu Wenyao, Xiao Jiayu, Yuan Cong, Chen Yaoxi, Guo Jianwei, Yue Hangbo, Zhu Dongyu, Lin Wenjing, Tang Shengqiu, Dong Xiaoying
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China.
Guangdong Provincial Key Lab of Green Chemical Product Technology, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
Pharmaceutics. 2020 Feb 18;12(2):170. doi: 10.3390/pharmaceutics12020170.
To decrease critical micelle concentration (CMC), improve stability, and keep high drug-loading capacity, three pH-sensitive mixed micelles applied for anticancer drug controlled delivery were prepared by the mixture of polymers poly (-diethylaminoethyl methacrylate)--poly(poly(ethylene glycol) methyl ether methacrylate) (PDEAEMA-PPEGMA) and polycaprolactone--poly (poly(ethylene glycol) methyl ether methacrylate) (PCL-PPEGMA), which were synthesized and confirmed by H NMR and gel permeation chromatographic (GPC). The critical micelle concentration (CMC) values of the prepared mixed micelles were low, and the micellar sizes and zeta potentials of the blank mixed micelles demonstrated good pH-responsive behavior. Combined experimental techniques with dissipative particle dynamics (DPD) simulation, the particle sizes, zeta potentials, drug loading content (LC), encapsulation efficiency (EE), aggregation morphologies, and doxorubicin (DOX) distribution of the mixed micelles were investigated, and the high DOX-loading capacity of the mixed micelles was found. Both in vitro DOX release profiles and DPD simulations of the DOX dynamics release process exhibited less leakage and good stability in neutral conditions and accelerated drug release behavior with a little initial burst in slightly acidic conditions. Cytotoxicity tests showed that the polymer PDEAEMA-PPEGMA and the blank mixed micelles had good biocompatibility, and DOX-loaded mixed micelles revealed certain cytotoxicity. These results suggest that the drug-loaded mixed micelles that consisted of the two polymers PDEAEMA-PPEGMA and PCL-PPEGMA can be new types of pH-responsive well-controlled release anticancer drug delivery mixed micelles.
为降低临界胶束浓度（CMC）、提高稳定性并保持高载药量，通过聚（甲基丙烯酸二乙氨基乙酯）-聚（聚乙二醇甲基醚甲基丙烯酸酯）（PDEAEMA-PPEGMA）和聚己内酯-聚（聚乙二醇甲基醚甲基丙烯酸酯）（PCL-PPEGMA）的聚合物混合物制备了三种用于抗癌药物控释的pH敏感混合胶束，这些聚合物通过核磁共振氢谱（H NMR）和凝胶渗透色谱（GPC）进行了合成和表征。所制备混合胶束的临界胶束浓度（CMC）值较低，空白混合胶束的胶束尺寸和zeta电位表现出良好的pH响应行为。结合耗散粒子动力学（DPD）模拟的实验技术，研究了混合胶束的粒径、zeta电位、载药量（LC）、包封率（EE）、聚集形态和阿霉素（DOX）分布，发现混合胶束具有较高的DOX载药量。体外DOX释放曲线和DOX动力学释放过程的DPD模拟均显示，在中性条件下泄漏较少且稳定性良好，在微酸性条件下有轻微的初始突释后药物释放行为加速。细胞毒性测试表明，聚合物PDEAEMA-PPEGMA和空白混合胶束具有良好的生物相容性，载DOX的混合胶束显示出一定的细胞毒性。这些结果表明，由PDEAEMA-PPEGMA和PCL-PPEGMA这两种聚合物组成的载药混合胶束可以成为新型的pH响应良好的控释抗癌药物递送混合胶束。
