Guangdong Provincial Key Lab of Green Chemical Product Technology, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
School of Chemical Engineering, Xiangtan University, Xiangtan 411105, China.
Soft Matter. 2019 Jan 28;15(4):546-558. doi: 10.1039/c8sm01941j. Epub 2019 Jan 15.
High micellar stability and well-performed drug loading and release are two conflicting factors for unimolecular micelles as an ideal drug delivery system. Achieving the formation of unimolecular micelles with short hydrophilic blocks is a challenging and promising approach to solve this bottleneck and limitation of current unimolecular micelle systems. In this work, dissipative particle dynamics (DPD) simulation is used to study the synergetic effect of crosslinking and electrostatic repulsion on stability of unimolecular micelles and to analyze the micro-mechanism and factors influencing this synergetic stabilization strategy. The strategy can generate unimolecular micelles with extremely high stability for various supramolecular polymers with short hydrophilic chains. Protonation of DEAEMA blocks leads to a large improvement in micellar hydrophilicity. The protonated middle layer further shrinks through crosslinking to produce the largest charge density, enlarging the electrostatic repulsion between colloidal particles. Additionally, the crosslinking and protonation treatment maximizes the extension degree of hydrophilic EO segments due to the increasing steric hindrance and poor compatibility between DEAHEMA and EO blocks. In this study, the relation between shrinkage degree of hydrophobic cores and stability of unimolecular micelles is first reported. The above-mentioned transition of micellar structures and properties results in the maximum degree of core shrinkage (R of MMA blocks) corresponding to the high stability of unimolecular micelles. Further study shows that the increasing cyclization degree, the mode of end cyclization, and the crosslinking and electrostatic repulsion of the middle layer all exert favorable effects on the stability of unimolecular micelles due to controlled shrinkage of hydrophobic cores.
高分子胶束的高胶束稳定性和良好的载药与释药性能是作为理想药物传递系统的单分子胶束的两个相互矛盾的因素。实现短亲水性链段的单分子胶束的形成是解决当前单分子胶束系统这一瓶颈和限制的具有挑战性和有前景的方法。在这项工作中，耗散粒子动力学（DPD）模拟被用来研究交联和静电排斥对单分子胶束稳定性的协同效应，并分析影响这种协同稳定策略的微观机制和因素。该策略可以为具有短亲水性链的各种超分子聚合物生成具有极高稳定性的单分子胶束。DEAEMA 链段的质子化导致胶束亲水性的大幅度提高。质子化的中间层通过交联进一步收缩，产生最大的电荷密度，增大胶体颗粒之间的静电排斥。此外，交联和质子化处理由于 DEAHEMA 和 EO 链段之间的空间位阻增加和相容性差，最大限度地增加了亲水 EO 段的伸展程度。在本研究中，首次报道了疏水性核的收缩程度与单分子胶束稳定性之间的关系。胶束结构和性质的上述转变导致疏水性核的最大收缩程度（MMA 链段的 R）对应于单分子胶束的高稳定性。进一步的研究表明，不断增加的环化程度、端环化的方式以及中间层的交联和静电排斥由于对疏水性核的受控收缩都对单分子胶束的稳定性产生有利影响。
