School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China.
School of Information Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, PR China.
Colloids Surf B Biointerfaces. 2019 Jun 1;178:56-65. doi: 10.1016/j.colsurfb.2019.02.043. Epub 2019 Feb 21.
In order to better understand and improve the drug loading capacity and release behavior of the pH-responsive mixed micelles in well controlled pH environments, dissipative particle dynamics (DPD) simulations are employed. This is performed by studying the co-micellization behavior of these materials produced from the two specific diblock polymers, poly(ethylene glycol) methyl ether-b-poly(N, N diethylamino ethyl methacrylate) (MPEG-PDEAEMA) and poly(ethylene glycol) methyl ether-b-polycaprolactone (MPEG-PCL) for doxorubicin (DOX) delivery. With the use of appropriate interaction parameters, the formation mechanism of (drug-loaded) mixed micelles, particle sizes, morphology, and composition are investigated. Simulation results show that compared with pure MPEG-PDEAEMA or MPEG-PCL, the mixed MPEG-PDEAEMA and MPEG-PCL system can combine to form multifunctional mixed micelles with larger particle sizes that lead to improved stability, higher drug loading capacity and better-controlled drug release performance. Simulations of the drug release process using the mixed micelles show that, when the environment is acidic, the tertiary amine group of PDEAEMA and DOX3 lead to rapid diffusion and release of the DOX in the aqueous solution. It is found that the presence of MPEG-PCL has a great influence in avoiding the fast release of the drug inside the core of micelles. Therefore, this study offers a deeper understanding of the mechanism on the co-micellization behaviors, the pH-responsive and drug controlled release behaviors of mixed micelles.
为了更好地理解和改善在精确控制的 pH 环境下 pH 响应性混合胶束的载药能力和释放行为，采用耗散粒子动力学（DPD）模拟来实现。这是通过研究由两种特定的两亲嵌段聚合物聚乙二醇甲基醚-b-聚（N，N-二乙基氨基乙基甲基丙烯酸酯）（MPEG-PDEAEMA）和聚乙二醇甲基醚-b-聚己内酯（MPEG-PCL）产生的这些材料的共胶束化行为来实现的，用于阿霉素（DOX）递送。通过使用适当的相互作用参数，研究了（载药）混合胶束的形成机制、粒径、形态和组成。模拟结果表明，与纯 MPEG-PDEAEMA 或 MPEG-PCL 相比，混合的 MPEG-PDEAEMA 和 MPEG-PCL 系统可以结合形成具有更大粒径的多功能混合胶束，从而提高了稳定性、更高的载药能力和更好的控制药物释放性能。使用混合胶束进行药物释放过程的模拟表明，当环境呈酸性时，PDEAEMA 的叔胺基团和 DOX3 导致 DOX 在水溶液中快速扩散和释放。结果发现，MPEG-PCL 的存在对避免药物在胶束核心内的快速释放有很大的影响。因此，这项研究深入了解了混合胶束的共胶束化行为、pH 响应性和药物控制释放行为的机制。
