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Design and characterization of polymeric micelles with entrapped peptides

包载肽的聚合物胶束的设计和表征

基本信息

批准号：
07558130
负责人：
KATAOKA Kazunori
金额：
$ 3.07万
依托单位：
Science University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

A variety of poly (ethylene glycol) (PEG) /polyamino acid block copolymers was synthesized by initiating the ring opening polymerization of alpha-amino acid N-carboxyanhydride (NCA) from primary amino group settled on the chain end of alpha-methoxy-omega-amino-poly (ethylene glycol). After the removal of protecting group, hydrophobic moieties were introduced into the side chain of poly (amino acid) segments of the block copolymer to control the hydrophilic/hydrophobic balance, allowing to form stable and monodispersive polymeric micelle. Micelles were prepared by solvent-substituting technique in the presence of peptide models to obtain peptide-loaded polymeric micelles. A fluorescent dye, pyrene, was used as a model compound for peptides. Dynamic light scattering measurements revealed a formation of micelles with relatively narrow distribution from block copolymers with considerably high substitution degree of side chain. These micelles had a very low critical micelle concentration (-30mg/l), indicating that they are thermodynamically stable. Of interest, in the case of block copolymers of PEG with poly (L-lysine) substituted with hydrocynnamic acid (HCA), secondary structure of poly (L-lysine) segments changed from random to beta-sheet upon micellization, indicating a close relationship between micelle formation and secondary structure of poly (amino acid) segments forming the core. Pyrene in the micelle was shown to be stably entrapped in the core, suggesting a promising feature of these micelles as novel peptide carriers.

以α-甲氧基-ω-氨基-聚乙二醇（PEG）为原料，通过引发α-氨基酸-N-羧酸酐（NCA）开环聚合，合成了聚乙二醇（PEG）/聚氨基酸嵌段共聚物。在去除保护基团后，将疏水部分引入到嵌段共聚物的聚（氨基酸）链段的侧链中以控制亲水/疏水平衡，从而允许形成稳定且单分散的聚合物胶束。在模拟肽的存在下，通过溶剂取代技术制备胶束，得到负载肽的聚合物胶束。荧光染料芘被用作肽的模型化合物。动态光散射测量显示，形成胶束与相对较窄的分布从嵌段共聚物具有相当高的侧链取代度。这些胶束具有非常低的临界胶束浓度（~ 30 mg/l），表明它们是化学稳定的。感兴趣的是，在PEG与用羟基肉桂酸（HCA）取代的聚（L-赖氨酸）的嵌段共聚物的情况下，聚（L-赖氨酸）片段的二级结构在胶束化后从无规变为β-折叠，表明胶束形成与形成核心的聚（氨基酸）片段的二级结构之间的密切关系。芘在胶束中被证明是稳定地截留在核心，这表明这些胶束作为新型肽载体的一个有前途的功能。