Long-circulating poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles with modulated surface charge
Long-circulating poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles with modulated surface charge
复制标题
DOI：
10.1016/s0168-3659(01)00451-5
复制
发表时间：
2001-11-09
影响因子：
10.8
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Yamamoto, Y;Nagasaki, Y;Kataoka, K
由α-缩醛-聚聚乙二醇（D，L-丙交酯）嵌段共聚物在本研究中制备了具有窄尺寸分布的聚（乙缩醛-PEG-PDLLA）以缀合小肽基配体酪氨酸（Tyr）和酪氨酰-谷氨酸（Tyr-Glu），通过在将α-乙缩醛基团转化为醛基之后的还原胺化，允许将胶束的表面电荷从中性（Tyr-）调节为阴离子（Tyr-Glu-）。这两种胶束在血室中的循环时间显著延长，即使在24 h时仍有25%的注射剂量循环。此外，与中性Tyr-缀合的胶束相比，阴离子Tyr-Glu-缀合的PEG-PDLLA胶束被证明明显降低了肝脏和脾脏的摄取，这表明胶束表面上的轻微阴离子电荷在避免非特异性器官摄取中的重要作用。通过凝胶过滤测定从注射胶束的小鼠在24小时收集的血浆样品，直接观察Tyr-PEG-PDLLA胶束在血液隔室中胶束形式的稳定性。这些结果表明，具有合适尺寸和窄分布性质的表面调节的PEG-PDLLA胶束具有作为具有期望的生物相容性和生物功能性的长循环载体系统的有希望的潜力。(C)2001 Elsevier Science B. V.保留所有权利。
Reactive polymeric micelles consisting of an alpha -acetal-poly(ethylene glycol) -poly(D,L-lactide) block copolymer (acetal-PEG-PDLLA) with a narrow size distribution were prepared in this study to conjugate small peptidyl ligands, tyrosine (Tyr) and tyrosyl-glutamic acid (Tyr-Glu), through reductive amination after converting the a-acetal group to an aldehyde group, allowing modulation of the surface charge of the micelles from neutral (Tyr-) to anionic (Tyr-Glu-). Both of these micelles showed a significantly long circulating time in the blood compartment with 25% of injected dose still circulating even at 24 h. Further, an appreciably lowered uptake into the liver and spleen was demonstrated for the anionic Tyr-Glu-conjugated PEG-PDLLA micelle compared with a neutral Tyr-conjugated micelle, suggesting a substantial role of the slight anionic charge on the micelle surface in avoiding non-specific organ uptake. Stability of the micelle form in the blood compartment was directly observed for the Tyr-PEG-PDLLA micelle by a gel filtration assay of a plasma sample collected from the micelle-injected mice at 24 h. These results demonstrated that a surface-modulated PEG-PDLLA micelle with a suitable size and a narrowly distributed nature has promising potential as a long-circulating carrier system with desirable biocompatibility and biofunctionality. (C) 2001 Elsevier Science B.V. All rights reserved.