School of Chemistry and Chemical Engineering, Guangdong Provincial Key Lab for Green Chemical Product Technology, South China University of Technology, Guangzhou 510640, P. R. China.
Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, United States.
Langmuir. 2021 Jan 26;37(3):1225-1234. doi: 10.1021/acs.langmuir.0c03217. Epub 2021 Jan 8.
Unimolecular micelles have attracted wide attention in the field of drug delivery because of their thermodynamic stability and uniform size distribution. However, their drug loading/release mechanisms at the molecular level have been poorly understood. In this work, the stability and drug loading/release behaviors of unimolecular micelles formed using generation-5 polyamidoamine-graft-poly(carboxybetaine methacrylate) (PAMAM(G5)-PCBMA) were studied by dissipative particle dynamics simulations. In addition, the unimolecular micelles formed using generation-5 polyamidoamine-graft-poly(ethyleneglycol methacrylate) (PAMAM(G5)-PEGMA) were used as a comparison. The simulation results showed that PAMAM(G5)-PCBMA can spontaneously form core-shell unimolecular micelles. The PAMAM(G5) dendrimer constitutes a hydrophobic core to load the doxorubicin (DOX), while the zwitterionic PCBMA serves as a protective shell to improve the stability of the unimolecular micelle. The DOX can be encapsulated into the cavity of PAMAM(G5) at the physiological pH 7.4. The drug loading efficiency and drug loading content showed some regularities with the increase in the drug concentration. At the acidic pH 5.0, the loaded DOX can be released gradually from the hydrophobic core. The comparison of DOX-loaded morphologies between the PAMAM(G5)-PCBMA system and PAMAM(G5)-PEGMA system showed that the former has better monodisperse stability. This work could offer theoretical guidance for the design and development of promising unimolecular micelles for drug delivery.
单分子胶束因其热力学稳定性和均匀的粒径分布而在药物传递领域引起了广泛关注。然而，其在分子水平上的药物加载/释放机制还了解甚少。在这项工作中，通过耗散粒子动力学模拟研究了由第五代聚酰胺-胺接枝-聚（羧基甜菜碱甲基丙烯酸酯）（PAMAM（G5）-PCBMA）形成的单分子胶束的稳定性和药物加载/释放行为。此外，还使用了由第五代聚酰胺-胺接枝-聚（乙二醇甲基丙烯酸酯）（PAMAM（G5）-PEGMA）形成的单分子胶束作为对比。模拟结果表明，PAMAM（G5）-PCBMA 可以自发形成核壳型单分子胶束。PAMAM（G5）树枝状大分子构成疏水性内核来装载阿霉素（DOX），而两性离子 PCBMA 则作为保护壳来提高单分子胶束的稳定性。在生理 pH 值 7.4 下，DOX 可以被包裹在 PAMAM（G5）的空腔中。药物载量效率和载药量随着药物浓度的增加表现出一定的规律性。在酸性 pH 值 5.0 下，负载的 DOX 可以从疏水性内核中逐渐释放。PAMAM（G5）-PCBMA 体系和 PAMAM（G5）-PEGMA 体系中负载 DOX 的形态比较表明，前者具有更好的单分散稳定性。这项工作为设计和开发用于药物传递的有前途的单分子胶束提供了理论指导。
