聚乙二醇/聚己内酯/聚乙烯亚胺载胰岛素纳米粒的体外释药性能  

Evaluation of in vitro insulin release from nanoparticles assembled by polyethylene glycol, polycaprolactone and polyethyleneimine

作　　者：王颐婷 李伟炜[1] 沈梅[2] 陈清元[1] 曾庆冰[1] 

机构地区：[1]南方医科大学药学院,广东广州510515 [2]南方医科大学公共卫生与热带医学学院卫生检测中心,广东广州510515

出　　处：《南方医科大学学报》2016年第1期109-115,共7页Journal of Southern Medical University

基　　金：广州市科技计划项目(12c32121550)

摘　　要：目的合成聚乙烯亚胺/聚己内酯/聚乙二醇/聚己内酯/聚乙烯亚胺(PEI-PCL-PEG-PCL-PEI),以其为载体制备聚合物载胰岛素(INS)缓释纳米粒,考察和优化其体外释药性能。方法利用迈克尔加成反应合成该聚合物,用傅里叶红外光谱(FT-IR)和核磁共振氢谱(1H-NMR)对其结构进行表征,荧光探针法测定其临界聚集浓度(CAC);采用溶剂挥发法制备聚合物载INS纳米粒,透射电镜观察其形态,激光散射法测定粒径及多分散指数,Bradford法测定载药情况并考察体外释放行为。结果以PEI10K-PCL4K-PEG2K-PCL4K-PEI10K为INS载体,投药比为40%wt时制备的载INS纳米粒药物利用度最大,包封率为(57.23±0.25)%,粒径为175.30±19.51 nm,48 h末的累计释放率为50.66%;此外还可通过调整聚合物不同嵌段的比例进一步降低药物突释效应。结论以PEI-PCL-PEG-PCL-PEI为载体制备的载INS纳米粒包封率、载药量较高,体外释药缓释效应明显且PEI的引入在一定程度上有助于减少突释效应。Objective To prepare insulin- loaded polymeric nanoparticles based on polyethyleneimine- polycaprolactonepolyethylene glycol- polycaprolactone- polyethyleneimine pentablock copolymers and evaluate its in vitro release of insulin.Methods Polycaprolactone-polyethylene glycol-polycaprolactone（PCL-PEG-PCL） triblock copolymer was synthesized by ringopening polymerization method, and the pentablock copolymer was prepared by Michael addition reaction. The copolymers obtained were characterized by Fourier- transform infrared（FT- IR） spectroscopy and1H- NMR and their critical aggregation concentration（CAC） was measured by fluorescence technique with pyrene as the probe. Insulin- loaded polymeric nanoparticles based on the pentablock copolymers were prepared by solvent evaporation method that exploited the cationic nature of PEI- PCL- PEG- PCL- PEI to allow the formation of ionic complexes with anionic biomolecules such as insulin. The prepared nanoparticles were further characterized by Malvern laser particle sizer and transmittion electron microscopy（TEM）.The drug loading, encapsulation efficiency and in vitro release profile of the nanoparticles were analyzed using Bradford method. Results Using copolymer PEI10K- PCL4K- PEG2K- PCL4K- PEI10 K as the drug carrier, the spherical nanoparticles prepared with an optimal insulin-coplymer mass ratio of 40% allowed the maximum insulin loading of（18.63±0.07）% and had an average particle size of 175.30±19.51 nm. The prepared nanoparticles was capable of sustained release of insulin for as long as 48 h in vitro, and the burst release could be minimized by incorporation of PEI in the triblock copolymer. Conclusion The insulin-loaded polymeric nanoparticles based on the pentablock copolymers allow sustained release of insulin in vitro, and PEI can enhance sustained drug release and reduce burst drug release.

关 键 词：聚乙烯亚胺/聚己内酯/聚乙二醇/聚己内酯/聚乙烯亚胺 胰岛素 纳米粒 体外释放 

分 类 号：O631.3[理学—高分子化学] TQ460.1[理学—化学]