School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China.
Department of Materials Science and Engineering, Rutgers University, Piscataway, NJ, 08854, USA.
Colloids Surf B Biointerfaces. 2019 Oct 1;182:110313. doi: 10.1016/j.colsurfb.2019.06.043. Epub 2019 Jul 9.
Intelligent reversible crosslinked micelles that have a good balance of structure stability in normal tissue and controlled drug release responded to the tumor microenvironment are highly promising novel drug delivery systems. However, to date, there have been very few reports about mesoscale simulations of drug-loaded polymeric reversible crosslinked micelles. Here, dissipative particle dynamics (DPD) simulation, the nearest-neighbor bonding principle, and the nearest media-bead bond breaking principle were used to investigate the influence of physiological environment along with low tumor pH and reduction microenvironment on the stability and doxorubicin (DOX) distribution of the star polymer [PCL-b-P(HEMA-Se-Se˜)-b-PPEGMA] diselenide crosslinked micelles with different diselenide crosslinking levels (CLs). The self-assembly process results obtained by DPD simulations reveal the formation of three-layer spherical micelles with the loaded DOX mainly distributed at the interfacial regions of the inner PCL core and middle HEMA layer. The structural stability and DOX loading capacity of the micelles can be improved by appropriately increasing the CL based on the nearest-neighbor bonding principle due to the effect of the pressure exerted by the crosslink that squeezes the loaded drugs from the intermediate and interfacial layers into the micelle core. Furthermore, the effect of breaking of the diselenide bond on the drug release properties was investigated through the use of the nearest media-bead bond breaking principle. A low CL gives rise to intense drug release, increasing the toxic side effects on the system. With the increase in the CL, the micelles show the transformation from local crosslinking to compact crosslinking, leading to slower drug release. Therefore, this work can provide some guidance on the mesoscale for the structural design and controlled construction of reversible crosslinked micelles for smart drug delivery systems.
具有良好的正常组织结构稳定性和可控药物释放能力的智能可逆交联胶束，能够响应肿瘤微环境，是一种很有前途的新型药物传递系统。然而，迄今为止，关于载药聚合物可逆交联胶束的介观模拟研究很少。在这里，耗散粒子动力学（DPD）模拟、最近邻键合原理和最近介质珠键断裂原理被用于研究生理环境以及低肿瘤 pH 值和还原微环境对具有不同二硒键交联水平（CL）的星型聚合物[PCL-b-P（HEMA-Se-Se˜）-b-PPEGMA]二硒键交联胶束的稳定性和阿霉素（DOX）分布的影响。DPD 模拟得到的自组装过程结果表明，形成了具有三层球形结构的胶束，载药 DOX 主要分布在内层 PCL 核和中层 HEMA 层的界面区域。根据最近邻键合原理，适当增加 CL 可以提高胶束的结构稳定性和载药能力，这是由于交联所产生的压力将载药从中间层和界面层挤压到胶束核内的缘故。此外，还通过使用最近介质珠键断裂原理研究了二硒键断裂对药物释放性能的影响。低 CL 会导致强烈的药物释放，增加系统的毒性副作用。随着 CL 的增加，胶束表现出从局部交联到紧密交联的转变，导致药物释放速度变慢。因此，这项工作可以为智能药物传递系统的可逆交联胶束的结构设计和控制构建提供一些介观指导。
