pH-sensitive unimolecular polymeric micelles: Synthesis of a novel drug carrier
pH-sensitive unimolecular polymeric micelles: Synthesis of a novel drug carrier
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DOI：
10.1021/bc020041f
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发表时间：
2003-07-01
影响因子：
4.7
通讯作者：
Leroux, JC
中科院分区：
文献类型：
--
作者：
Jones, MC;Ranger, M;Leroux, JC
采用原子转移自由基聚合法合成了具有pH敏感性的两亲性星形聚合物。这些新的聚合物呈现出类似于聚合物胶束的核-壳结构，但固有地对稀释稳定，并且被称为单分子聚合物胶束。采用四臂多功能引发剂对疏水性的甲基丙烯酸乙酯、甲基丙烯酸叔丁酯和亲水性的聚乙二醇甲基丙烯酸酯进行了序列聚合。聚合物的分子量范围从9000至20000获得。动态光散射结果表明胶束粒径在11 ~ 40 nm之间。单分子胶束也分析了静态光散射在水环境中。疏水单体摩尔比最高的星形聚合物倾向于在水中形成高分子量聚集体。甲基丙烯酸叔丁酯单元的水解允许引入可电离的甲基丙烯酸官能团。尺寸分布是双峰在酸性和碱性pH值。因为，聚合物被设计为潜在的口服给药系统的疏水性药物，它们被滴定，以评估作为pH值的函数的电离度。在胃中，羧基功能预计将被完全质子化。然而，在肠道中，胶束将超过40%电离。进行荧光研究以评价胶束核的极性。结果表明，随着pH值的极性增加，由于电离的酸功能存在沿着聚合物链。pH值的升高与孕酮的体外释放速率的增加有关，孕酮被用作疏水药物模型。
Novel amphiphilic star-shaped polymers showing pH-sensitivity were synthesized by atom transfer radical polymerization. These new polymers present a core-shell structure similar to polymeric micelles, but are inherently stable to dilution and are referred to as unimolecular polymeric micelles. A four-armed multifunctional initiator was used for the sequential polymerization of hydrophobic ethyl methacrylate and tert-butyl methacrylate and hydrophilic poly(ethylene glycol)methacrylate. Polymers of molecular weight ranging from 9000 to 20 000 were obtained. Results of dynamic light scattering showed micelle size ranging from 11 to 40 nm. Unimolecular micelles were also analyzed by static light scattering in aqueous environment. Star-shaped polymers which presented the highest molar ratio of hydrophobic monomers tended to form high molecular weight aggregates in water. Hydrolysis of the tert-butyl methacrylate units permitted the introduction of ionizable methacrylic acid functions. Size distributions were bimodal at both acidic and basic pH. Since, the polymers were designed as potential delivery systems for the oral administration of hydrophobic drugs, they were titrated to evaluate the degree of ionization as a function of pH. In the stomach, the carboxylic functions are expected to be fully protonated. However, in the intestine, the micelles will be more than 40% ionized. Fluorescence studies were conducted in order to evaluate the polarity of the micellar core. Results showed an increase in polarity with pH due to the ionization of the acid functions present along the polymer chains. The pH rise was associated with an increase in the in vitro release rate of progesterone, which was used as hydrophobic drug model.