Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Macromol Biosci. 2009 Dec 8;9(12):1219-26. doi: 10.1002/mabi.200900298.
In this study, a KRGDKK (Lys-Arg-Gly-Asp-Lys-Lys) peptide with a RGD sequence is utilized as a functional group to synthesize a novel thermo-sensitive hydrogel. The KRGDKK peptide prepared by a solid phase synthesis approach is coupled to the ends of a poly[(epsilon-caprolactone)-co-lactide]-poly(ethylene glycol)-poly[(epsilon-caprolactone)-co-lactide] (PCLA-PEG-PCLA) triblock copolymer to obtain peptide-PCLA-PEG-PCLA-peptide. The self-assembly behavior of both PCLA-PEG-PCLA and peptide-PCLA-PEG-PCLA-peptide copolymers in aqueous solution is investigated, and hydrogels prepared from PCLA-PEG-PCLA and peptide-PCLA-PEG-PCLA-peptide are also prepared. An in vitro cell viability study demonstrated that the peptide-PCLA-PEG-PCLA-peptide hydrogels do not exhibit an apparent cytotoxicity, which suggests that the hydrogels have promising potential as injectable drug-delivery systems. Furthermore, compared with the PCLA-PEG-PCLA hydrogels, the peptide-PCLA-PEG-PCLA-peptide hydrogels display improved mechanical properties because of hydrogen bonding between the amino groups of KRGDKK. An in vitro drug release study showed that the peptide-PCLA-PEG-PCLA-peptide hydrogels exhibit outstanding controlled release properties and the release of the drug could be sustained for more than a month without initial burst.
在这项研究中，利用含有 RGD 序列的 KRGDKK（赖氨酰-精氨酰-甘氨酰-天冬氨酰-赖氨酰-赖氨酰）肽作为功能基团来合成新型温敏水凝胶。通过固相合成方法制备的 KRGDKK 肽与聚[（ε-己内酯）-co-丙交酯]-聚乙二醇-聚[（ε-己内酯）-co-丙交酯]（PCLA-PEG-PCLA）三嵌段共聚物的两端偶联，得到肽-PCLA-PEG-PCLA-肽。研究了 PCLA-PEG-PCLA 和肽-PCLA-PEG-PCLA-肽共聚物在水溶液中的自组装行为，并制备了 PCLA-PEG-PCLA 和肽-PCLA-PEG-PCLA-肽共聚物的水凝胶。体外细胞活力研究表明，肽-PCLA-PEG-PCLA-肽水凝胶没有明显的细胞毒性，这表明水凝胶作为可注射药物递送系统具有很大的应用潜力。此外，与 PCLA-PEG-PCLA 水凝胶相比，由于 KRGDKK 中的氨基之间的氢键作用，肽-PCLA-PEG-PCLA-肽水凝胶表现出改善的机械性能。体外药物释放研究表明，肽-PCLA-PEG-PCLA-肽水凝胶具有出色的控制释放性能，药物的释放可以持续一个月以上而没有初始突释。
