Nakagawa Yasuhiro, Ushidome Kotaro, Masuda Keita, Igarashi Kazunori, Matsumoto Yu, Yamasoba Tatsuya, Anraku Yasutaka, Takai Madoka, Cabral Horacio
Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
Polymers (Basel). 2023 Jun 9;15(12):2626. doi: 10.3390/polym15122626.
Multi-arm star-shaped block copolymers with precisely tuned nano-architectures are promising candidates for drug delivery. Herein, we developed 4- and 6-arm star-shaped block copolymers consisting of poly(furfuryl glycidol) (PFG) as the core-forming segments and biocompatible poly(ethylene glycol) (PEG) as the shell-forming blocks. The polymerization degree of each block was controlled by adjusting the feeding ratio of a furfuryl glycidyl ether and ethylene oxide. The size of the series of block copolymers was found to be less than 10 nm in DMF. In water, the polymers showed sizes larger than 20 nm, which can be related to the association of the polymers. The star-shaped block copolymers effectively loaded maleimide-bearing model drugs in their core-forming segment with the Diels-Alder reaction. These drugs were rapidly released upon heating via a retro Diels-Alder step. When the star-shaped block copolymers were injected intravenously in mice, they showed prolonged blood circulation, with more than 80% of the injected dose remaining in the bloodstream at 6 h after intravenous injection. These results indicate the potential of the star-shaped PFG-PEG block copolymers as long-circulating nanocarriers.
具有精确调控纳米结构的多臂星形嵌段共聚物是很有前景的药物递送候选材料。在此，我们制备了由聚（糠醇缩水甘油）（PFG）作为核心形成段和生物相容性聚（乙二醇）（PEG）作为壳形成嵌段组成的四臂和六臂星形嵌段共聚物。通过调节糠醇缩水甘油醚和环氧乙烷的进料比来控制每个嵌段的聚合度。发现该系列嵌段共聚物在N，N - 二甲基甲酰胺中的尺寸小于10nm。在水中，聚合物的尺寸大于20nm，这可能与聚合物的缔合有关。星形嵌段共聚物通过狄尔斯 - 阿尔德反应在其核心形成段有效地负载了含马来酰亚胺的模型药物。这些药物通过逆狄尔斯 - 阿尔德步骤在加热时迅速释放。当星形嵌段共聚物静脉注射到小鼠体内时，它们表现出延长的血液循环时间，静脉注射后6小时超过80％的注射剂量仍留在血液中。这些结果表明星形PFG - PEG嵌段共聚物作为长循环纳米载体的潜力。
