Polypeptoid-block-polypeptide Copolymers: Synthesis, Characterization, and Application of Amphiphilic Block Copolypept(o)ides in Drug Formulations and Miniemulsion Techniques
Polypeptoid-block-polypeptide Copolymers: Synthesis, Characterization, and Application of Amphiphilic Block Copolypept(o)ides in Drug Formulations and Miniemulsion Techniques
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DOI：
10.1021/bm401542z
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发表时间：
2014-02-01
影响因子：
6.2
通讯作者：
Barz, Matthias
中科院分区：
文献类型：
--
作者：
Birke, Alexander;Huesmann, David;Barz, Matthias
本文报道了聚精氨酸-嵌段聚谷氨酸苄酯（PSar-block-PGlu(OBn)）和聚精氨酸-嵌段聚赖氨酸- ε - n-苯氧羰基（PSar-block-PLys(Z)）共聚物的合成。采用开环聚合（ROP）法制备了n -羧基氢化物（NCAs）的新型多肽-嵌段多肽共聚物（共聚物）。从保护基团、嵌段序列和长度三个方面对聚合条件进行了优化。而聚合度的PSar块长度设置在200或400左右，PGlu（OBn）和PLys(Z)块长度变化在20至75之间。所得嵌段共聚物的总聚合度在220 ~ 475之间，分散指数在1.1 ~ 1.2之间。新型嵌段共聚物在HEK293细胞中高达3mg /mL的无毒行为，已应用于有机胶体的合成（通过微乳液聚合和微乳液溶剂蒸发工艺）。制备了粒径在100 ~ 200 nm之间的胶体（微乳液聚合）。此外，PSar-block-PGlu（OBn）共聚物已用于腺苷酸环化酶抑制剂的药物配方中。荧光相关光谱（FCS）观察到胶束直径分别为28.0 nm（未加药）和33.0 nm（加药）。多肽阻断多肽制剂增加了药物的溶解度并提高了其生物利用度，从而导致MaMel 91黑色素瘤细胞内cAMP水平的降低。
We report the synthesis of polysarcosine-block-polyglutamic acid benzylester (PSar-block-PGlu(OBn)) and polysarcosine-block-polylysine-epsilon-N-benzyloxycarbonyl (PSar-block-PLys(Z)) copolymers. The novel polypeptoid-block-polypeptide copolymers (Copolypept(o)ides) have, been synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs). Polymerization conditions were optimized regarding protecting groups, block sequence and length. While the degree of polymerization of the PSar block length was set to be around 200 or 400, PGlu(OBn) and PLys(Z) block lengths were varied between 20 to 75. The obtained block copolymers had a total degree of polymerization of 220-475 and dispersity indices between 1.1 and 1.2. Having ensured a nontoxic behavior Up to a concentration of 3 mg/mL in HEK293 cells, the novel block copolymers have been applied to the synthesis of organic colloids (by miniemulsion polymerization and miniemulsion solvent evaporation process). Colloids of around 100 nm (miniemulsion polymerization) to 200 nm (miniemulsion process) have been prepared. Additionally, PSar-block-PGlu(OBn) copolymers have been used in a drug formulation of an adenylate cyclase inhibitor. Micelles of 28.0 nm (without drug) and 33.0 nm (with drug) diameter have been observed by fluorescence correlation spectroscopy (FCS). The polypeptoid-block-polypeptide formulation increased solubility of the drug and enhances its bioavailability, which leads to a reduction of intracellular cAMP levels in MaMel 91 melanoma cells.