重组人肿瘤坏死因子隐形纳米粒的制备及其稳定性  

Preparation and stability of recombinant human tumor necrosis factor-α-loaded stealth nanoparticles

作　　者：方超[1] 施斌[1] 裴元英[1] 

机构地区：[1]复旦大学药学院药剂教研室,上海200032

出　　处：《药学学报》2004年第11期939-943,共5页Acta Pharmaceutica Sinica

基　　金：上海市科技发展基金项目 (0 2 43nm0 67) .

摘　　要：目的　制备 3种不同粒径和表面为 3种不同分子量 (2 0 0 0 ,5 0 0 0和 10 0 0 0 )的单甲氧基聚乙二醇 (MePEG)修饰的重组人肿瘤坏死因子隐形纳米粒 ,考察纳米粒胶体溶液的稳定性。方法　合成载体材料聚乙二醇化聚十六烷基氰基丙烯酸酯 (MePEG PHDCA)和聚十六烷基氰基丙烯酸酯 (PHDCA) ,用FTIR ,1 HNMR ,1 3CNMR和GPC技术对其表征。以均匀设计法优化制备各类隐形和普通纳米粒。将纳米粒胶体溶液在 2 - 8℃存放 4周 ,观察粒径变化。结果　FTIR ,1 HNMR ,1 3CNMR图谱与MePEG PHDCA和PHDCA的结构相符 ,GPC表明两类载体材料分子量分布较窄。纳米粒包封率较高 ,粒径分别约为 80 ,170和 2 4 0nm。 4周内 ,纳米粒粒径未见显著变化。结论MePEG PHDCA和PHDCA合成成功。制备的纳米粒在水溶液中不易发生显著聚集、整体溶蚀或表面溶蚀降解 ,纳米粒稳定性较好。Aim To prepare recombinant human tumor necrosis factor-α (rHuTNF-α)-loaded stealth nanoparticles with different PEG chain lengths and sizes, and investigate the stability of nanoparticle suspensions. Methods The poly(MePEG cyanoacrylate-co-hexadecyl cyanoacrylate) (MePEG-PHDCA) and poly(hexadecyl cyanoacrylate) (PHDCA) were synthesized and characterized with Fourier transform infrared spectrum (FTIR), 1HNMR, 13CNMR and gel permeation chromatography (GPC). Uniform design was used to optimize the entrapment efficiency. The nanoparticle suspensions were stored at 2- 8 ℃ for 4 weeks, and the particle size evolution was studied. Results FTIR, 1HNMR and 13CNMR were consistent with the structures of MePEG-PHDCA and PHDCA whose polydispersity indexes were all less than 1.1, indicating narrow distributions. The entrapment efficiency of all nanoparticles was satisfactory. The three different mean diameters of MePEG-PHDCA and PHDCA nanoparticles were about 80 nm, 170 nm and 240 nm, separately. The nanoparticle suspensions maintained their sizes at 2- 8 ℃ for 4 weeks Conclusion MePEG-PHDCA with three different molecular weight MePEG and PHDCA were synthesized successfully. There are negligible aggregations and bulk or surface erosion as for both stealth MePEG-PHDCA and conventional PHDCA nanoparticles in distilled water.

关 键 词：重组人肿瘤坏死因子 隐形纳米粒 长循环纳米粒 均匀设计 

分 类 号：R943.3[医药卫生—药剂学]