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Fabrication of PDEAEMA-based pH-responsive mixed micelles for application in controlled doxorubicin release

机译：基于PDEAEMA的pH响应混合胶束的制备，可用于受控的阿霉素释放

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Co-micellization of the diblock polymers poly(ethylene glycol) methyl ether-b-poly(N,N-diethylaminoethyl methacrylate) (MPEG–PDEAEMA) and poly(ethylene glycol) methyl ether-b-polycaprolactone (MPEG–PCL) was carried out to avoid the complicated synthetic steps of a single polymer and enhance the drug loading contents as well as the pH-responsive drug release performances of the polymers. The molecular weight and molecular structure of MPEG–PDEAEMA and MPEG–PCL were measured and confirmed by gel permeation chromatography (GPC) and 1H NMR. With the mass ratio of MPEG–PCL and MPEG–PDEAEMA set at 1?:?3, all three mixed micelles, MIX1 (MPEG–PCL40 and MPEG–PDEAEMA20), MIX2 (MPEG–PCL60 and MPEG–PDEAEMA35), and MIX3 (MPEG–PCL80 and MPEG–PDEAEMA50), showed good stability and excellent pH-responsive performances according to their critical micellar concentrations (CMC), particle sizes, and zeta potentials. The doxorubicin (DOX) loading content (LC) and entrapment efficiency (EE) of the micelles were 26.79% and 63.19% (MIX1), 22.81% and 59.03% (MIX2), and 21.46% and 54.65% (MIX3), respectively. As the PDEAEMA/PCL content increased, the drug loading content decreased, which was further confirmed by dissipative particle dynamics (DPD) simulations. The results indicate that the mixed micelles developed in this study might have some advantages in improving the drug loading capacity of the polymers. The drug release profiles demonstrate that the mixed micelles have excellent ability for the controlled release of DOX, suggesting great potential for application of the micellar systems in drug delivery, especially in the area of pH-targeted tumor treatment.
机译：二嵌段聚合物聚（乙二醇）甲醚- b -聚（ N ， N -甲基丙烯酸二乙氨基乙酯）的共胶束化（MPEG–进行了PDEAEMA）和聚（乙二醇）甲基醚- b -聚己内酯（MPEG-PCL）的操作，从而避免了单一聚合物的复杂合成步骤，并提高了载药量和pH聚合物的响应药物释放性能。通过凝胶渗透色谱法（GPC）和 1 H NMR测定并确认了MPEG–PDEAEMA和MPEG–PCL的分子量和分子结构。将MPEG–PCL和MPEG–PDEAEMA的质量比设置为1？：？3，所有三个混合胶束MIX1（MPEG–PCL 40 和MPEG–PDEAEMA < small> 20 ），MIX2（MPEG–PCL 60 和MPEG–PDEAEMA 35 ）和MIX3（MPEG–PCL 80 和MPEG–PDEAEMA 50 ）显示根据其临界胶束浓度（CMC），粒径和Zeta电位，具有良好的稳定性和出色的pH响应性能。胶束的阿霉素（DOX）负载量（LC）和包封效率（EE）分别为26.79％和63.19％（MIX1），22.81％和59.03％（MIX2），21.46％和54.65％（MIX3）。随着PDEAEMA / PCL含量的增加，载药量的下降，这通过耗散粒子动力学（DPD）模拟得到了进一步证实。结果表明，本研究开发的混合胶束在提高聚合物的载药量方面可能具有一些优势。药物释放曲线表明，混合的胶束具有出色的DOX控释能力，这表明胶束系统在药物传递中具有巨大潜力，特别是在以pH值为靶标的肿瘤治疗领域。

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