Design and characterization of polymeric micelles with entrapped peptides

以α-甲氧基-欧米伽-氨基-聚乙二醇链末端的伯氨基为起始基团，引发α-氨基酸N-羧酸酐(NCA)的开环聚合，合成了多种聚乙二醇(PEG)/多氨基酸嵌段共聚物。在去掉保护基后，在嵌段共聚物的多(氨基酸)链段的侧链中引入疏水基团来控制亲水/疏水平衡，从而形成稳定的单分散聚合物胶束。在多肽模型存在的情况下，通过溶剂取代技术制备胶束，以获得载多肽的聚合物胶束。一种名为芘的荧光染料被用作多肽的模型化合物。动态光散射测量表明，侧链取代度较高的嵌段共聚物形成了分布较窄的胶束。这些胶束的临界胶束浓度很低(-30 mg/L)，表明它们在热力学上是稳定的。值得注意的是，在聚乙二醇聚L赖氨酸被氢氰尿酸取代的嵌段共聚物中，聚L赖氨酸链段的二级结构在胶束化后从随机结构转变为β片层结构，表明胶束的形成与形成核的多氨基酸链段的二级结构密切相关。胶束中的芘被稳定地包裹在核心中，这表明这些胶束作为新型多肽载体的一个很有前途的特征。

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.