Shiraishi Kouichi, Yusa Shin-Ichi, Ito Masanori, Nakai Keita, Yokoyama Masayuki
Medical Engineering Laboratory, Research Center for Medical Sciences, The Jikei University School of Medicine, 163-1, Kashiwashita, Kashiwa, Chiba 277-0004, Japan.
Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan.
Polymers (Basel). 2017 Dec 14;9(12):710. doi: 10.3390/polym9120710.
We used photo irradiation to design core crosslinked polymeric micelles whose only significant physico-chemical change was in their physico-chemical stability, which helps elucidate poly(ethylene glycol) (PEG)-related immunogenicity. Synthetic routes and compositions of PEG--poly(aspartic acid) block copolymers were optimized with the control of -alkyl chain length and photo-sensitive chalcone moieties. The conjugation ratio between -alkyl chain and the chalcone moieties was controlled, and upon the mild photo irradiation of polymeric micelles, permanent crosslink proceeded in the micelle cores. In the optimized condition, the core crosslinked (CCL) micelles exhibited no dissociation while the non-CCL micelles exhibited dissociation. These results indicate that the photo-crosslinking reactions in the inner core were successful. A gel-permeation chromatography (GPC) measurement revealed a difference between the micellar-formation stability of CCL micelles and that of the non-CCL micelles. GPC experiments revealed that the CCL micelles were more stable than the non-CCL micelles. Our research also revealed that photo-crosslinking reactions did not change the core property for drug encapsulation. In conclusion, the prepared CCL micelles exhibited the same diameter, the same formula, and the same inner-core properties for drug encapsulation as did the non-CCL micelles. Moreover, the CCL micelles exhibited non-dissociable micelle formation, while the non-CCL micelles exhibited dissociation into single block copolymers.
我们利用光辐照设计了核交联聚合物胶束，其唯一显著的物理化学变化在于物理化学稳定性，这有助于阐明聚乙二醇（PEG）相关的免疫原性。通过控制烷基链长度和光敏查尔酮部分，优化了PEG - 聚天冬氨酸嵌段共聚物的合成路线和组成。控制了烷基链与查尔酮部分之间的共轭比，在对聚合物胶束进行温和光辐照时，胶束核内发生了永久性交联。在优化条件下，核交联（CCL）胶束未表现出解离，而非CCL胶束则表现出解离。这些结果表明内核中的光交联反应是成功的。凝胶渗透色谱（GPC）测量揭示了CCL胶束与非CCL胶束在胶束形成稳定性方面的差异。GPC实验表明CCL胶束比非CCL胶束更稳定。我们的研究还表明光交联反应不会改变药物包封的核性质。总之，所制备的CCL胶束与非CCL胶束具有相同的直径、相同的配方以及相同的药物包封内核性质。此外，CCL胶束表现出不可解离的胶束形成，而非CCL胶束则解离为单个嵌段共聚物。
