School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, P. R. China.
Jieyang Branch of Chemistry and Chemical Engineering Guangdong Laboratory (Rongjiang Laboratory), Jieyang 515200, China.
Langmuir. 2023 Nov 21;39(46):16358-16366. doi: 10.1021/acs.langmuir.3c02077. Epub 2023 Nov 7.
To enhance the stability of the polymeric micelles and optimize their drug-controlled release ability, three disulfide-linked polyethylene glycol methyl ether methacrylate-disulfide-poly(ε-caprolactone--γ-amine-ε-caprolactone) (PPEGMA-SS-P(CL--ACL)) polymers were synthesized and characterized by H NMR, GPC, and FT-IR successfully, and their dual pH/reduction-responsive cross-linked polymeric micelles were prepared for paclitaxel (PTX) delivery by using 2,3-dimethylmaleic anhydride (DMMA) as the cross-linking agent. The PTX loading capacity (LC) and encapsulation efficiency (EE) values of the cross-linked micelles formed by PPEGMA-SS-P(CL--ACL) achieved were 23.96% and 71.58%, slightly higher than those of un-cross-linked micelles. Both particle sizes of blank micelles and drug release of PTX-loaded micelles confirmed that compared with those un-cross-linked micelles, the cross-linked micelles were more stable at pH 7.4 + 0 mM DTT, with a PTX cumulative release of 13% at 120 h, while the PTX cumulative release of the cross-linked micelles at pH 5.0 + 10 mM DTT were close to that of un-cross-linked micelles after 60 h, indicating the successful reversible cross-linking and smooth drug release of the cross-linked micelles. The cytotoxicity assay showed that PPEGMA-SS-P(CL--ACL) and its cross-linked micelles had low cell cytotoxicity, and both PTX-loaded micelles revealed a certain inhibitory effect on HepG2 cells. These results revealed that the dual pH/reduction-responsive cross-linked polymeric micelles prepared from PPEGMA-SS-P(CL--DCL) were a promising candidate for PTX delivery.
为了提高聚合物胶束的稳定性并优化其药物控制释放能力，成功合成并通过核磁共振波谱仪（H NMR）、凝胶渗透色谱（GPC）和傅里叶变换红外光谱（FT-IR）对三种二硫键连接的聚乙二醇甲基醚甲基丙烯酸酯-二硫键-聚（ε-己内酯-γ-胺-ε-己内酯）（PPEGMA-SS-P（CL--ACL））聚合物进行了表征，并使用 2,3-二甲基马来酸酐（DMMA）作为交联剂制备了用于紫杉醇（PTX）递送的双 pH/还原响应交联聚合物胶束。由 PPEGMA-SS-P（CL--ACL）形成的交联胶束的紫杉醇载药量（LC）和包封效率（EE）值分别为 23.96%和 71.58%，略高于未交联胶束的值。空白胶束的粒径和载药胶束的药物释放均证实，与未交联胶束相比，在 pH 7.4 + 0 mM DTT 下，交联胶束更为稳定，在 120 h 时 PTX 的累积释放率为 13%，而在 pH 5.0 + 10 mM DTT 下，交联胶束的 PTX 累积释放率在 60 h 后接近未交联胶束，表明交联胶束的可逆交联和药物释放顺利。细胞毒性试验表明，PPEGMA-SS-P（CL--ACL）及其交联胶束的细胞毒性较低，载药胶束对 HepG2 细胞均表现出一定的抑制作用。这些结果表明，由 PPEGMA-SS-P（CL--DCL）制备的双 pH/还原响应交联聚合物胶束是一种有前途的紫杉醇递送载体。
