College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Langmuir. 2020 Mar 3;36(8):2082-2092. doi: 10.1021/acs.langmuir.9b03936. Epub 2020 Feb 23.
The self-assembly of a nonionic triblock copolymer (F127) and a nonionic surfactant (HS15) has been investigated due to favorable changes in properties in their mixtures. The effect of the mixing ratio on the self-assembly process and on the structural stability of the mixtures was studied by coarse-grained molecular dynamic simulation (CGMD) and experimental measurements (transmission electron microscopy, dynamic light scattering measurement, drug loading stability analysis, and fluorescence spectroscopy measurement). The CGMD provided the information on self-assembly behavior. The microstructure and micellar stability are affected by different proportions of F127/HS15. Pure HS15 molecules (system I) can rapidly form stable aggregates driven by strong hydrophobic force, including two steps: the formation of seed clusters and the fusion of them. At low F127 ratio (system II), the self-assembly process is dynamic unstable, and a volatile "coil/cluster-like" aggregate is formed under the single "binding" effect. As the ratio of added F127 increase, such as system III, stable "lotus-seedpod-like" aggregates form under the double effects of "binding plus wrapping". Its dynamic equilibrium can be achieved rapidly. The experimental results approved the assumption of "different mixing ratio with different structural stability" and even different loading stability of F127/HS15 systems for drugs with different log , such as PUE and DTX, which means different loading area for them in the micellar systems at different mixing ratios because of less hydrophobic microdomains with the increase of F127 molecules.
由于混合物性质的有利变化，研究了非离子三嵌段共聚物（F127）和非离子表面活性剂（HS15）的自组装。通过粗粒化分子动力学模拟（CGMD）和实验测量（透射电子显微镜、动态光散射测量、药物负载稳定性分析和荧光光谱测量）研究了混合比对自组装过程和混合物结构稳定性的影响。CGMD 提供了自组装行为的信息。微结构和胶束稳定性受 F127/HS15 不同比例的影响。纯 HS15 分子（体系 I）可以在强疏水力的驱动下迅速形成稳定的聚集体，包括两个步骤：种子簇的形成和它们的融合。在低 F127 比例（体系 II）下，自组装过程是动态不稳定的，在单一“结合”效应下形成易挥发的“线圈/类簇”聚集体。随着添加 F127 比例的增加，例如体系 III，在“结合加包裹”的双重作用下形成稳定的“莲心豆荚状”聚集体。它可以迅速达到动态平衡。实验结果证实了“不同混合比具有不同结构稳定性”甚至 F127/HS15 体系对不同 log 值药物（如 PUE 和 DTX）具有不同负载稳定性的假设，这意味着由于 F127 分子的增加，它们在不同混合比的胶束体系中的不同疏水区中具有不同的负载面积。
