Kamei S, Kopecek J
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City 84112, USA.
Pharm Res. 1995 May;12(5):663-8. doi: 10.1023/a:1016247206531.
Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) containing one amino end-group and differing in molecular weight were synthesized by radical polymerization in the presence of 2-aminoethanethiol (AET) as chain transfer agent. These polymers were covalently attached via amide bonds to the surface of nanospheres based on a copolymer of methyl methacrylate, maleic anhydride, and methacrylic acid. When compared to unmodified nanospheres, those with the surface modified with ST-PHPMA possessed a decreased protein (albumin, IgG, fibrinogen) adsorption in vitro, an increased intravascular half-life as well as a decreased accumulation in the liver after intravenous administration into rats. The higher the molecular weight of the ST-PHPMA, the more pronounced the changes in these properties. The results obtained have clearly demonstrated that covalently attached ST-PHPMA chains are efficient in decreasing the biorecognition of negatively charged (hydrophilic) polymer surfaces.
以2-氨基乙硫醇（AET）作为链转移剂，通过自由基聚合反应合成了含有一个氨基端基且分子量不同的半遥爪聚[N-(2-羟丙基)甲基丙烯酰胺]（ST-PHPMA）。这些聚合物通过酰胺键与基于甲基丙烯酸甲酯、马来酸酐和甲基丙烯酸的共聚物的纳米球表面共价连接。与未修饰的纳米球相比，表面用ST-PHPMA修饰的纳米球在体外具有降低的蛋白质（白蛋白、免疫球蛋白G、纤维蛋白原）吸附、延长的血管内半衰期以及静脉注射到大鼠体内后肝脏中积累的减少。ST-PHPMA的分子量越高，这些性质的变化就越明显。所获得的结果清楚地表明，共价连接的ST-PHPMA链在降低带负电荷（亲水性）聚合物表面的生物识别方面是有效的。
