粒径和MePEG相对分子质量对隐形纳米粒体外巨噬细胞吞噬和大鼠体内长循环的影响  

Influence of particle size and MePEG molecular weight on in vitro macrophage uptake and in vivo long circulating of stealth nanoparticles in rats

作　　者：方超[1] 施斌[2] 洪鸣凰[2] 裴元英[2] 陈红专[1] 

机构地区：[1]上海交通大学基础医学院药理教研室,上海200025 [2]复旦大学药学院药剂教研室,上海200032

出　　处：《药学学报》2006年第4期305-312,共8页Acta Pharmaceutica Sinica

基　　金：上海市科技发展基金资助项目(0243nm067).

摘　　要：目的考察粒径和单甲氧基聚乙二醇(m ethoxypolyethyleneglycol,M ePEG)相对分子质量对重组人肿瘤坏死因子(recomb inant hum an tumor necrosis factor-,αrHuTNF-α)隐形纳米粒体外巨噬细胞吞噬和大鼠体内长循环的影响。方法复乳法制备3种不同粒径(约为80,170和240 nm)和表面用3种不同相对分子质量M ePEG(Mr为2 000,5 000和10 000)修饰的重组人肿瘤坏死因子聚乙二醇化聚十六烷基氰基丙烯酸酯[poly(m ethoxypolyethyleneglycolcyanoacrylate-co-n-hexadecyl cyanoacrylate),PEG-PHDCA]隐形纳米粒。进行不同纳米粒体外巨噬细胞吞噬和大鼠体内药代动力学试验,并加以比较。结果粒径相同时,随着M ePEG相对分子质量的增加,巨噬细胞吞噬量减小,血浆半衰期延长;相同M ePEG(Mr=5 000)修饰时,随着粒径的减小,巨噬细胞吞噬量减小,大鼠血浆半衰期延长。粒径和M ePEG相对分子质量与隐形纳米粒体外巨噬细胞摄取和大鼠体内长循环性质间有良好的线性相关性。其中,PEG5 000-PHDCA纳米粒(80.0 nm)体外减小巨噬细胞吞噬和大鼠体内长循环的能力最强。结论实验范围内,粒径和M ePEG相对分子质量对重组人肿瘤坏死因子隐形纳米粒体外巨噬细胞吞噬和大鼠体内长循环有显著影响。Aim To investigate the influence of particle size and methoxypolyethyleneglycol （MePEG） molecular weight on the in vitro macrophage uptake and in vivo long circulating of recombinant human tumor necrosis factor-α （rHuTNF-α）-loaded stealth nanoparticles in rats. Methods Three sizes （approximately 80, 70 and 240 nm） of poly （methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate） （PEG-PHDCA） nanoparticles loading rHuTNF-α were prepared at different MePEG molecular weights （Mr 2 000, 5 000, 10 000） using the double emulsion method. The in vitro macrophage uptake and in vivo long circulating properties in rats were examined and compared. Results The uptake by macrophages decreased and the half-life of rHuTNF-α in rat increased with the increase of MePEG molecular weight or the decrease of particle size. The linear-ships between particle size and MePEG molecular weight and the in vitro macrophage uptake and in vivo long circulating properties were fairly good. Having the highest MePEG surface density （1.32 nm ^-2）, the shortest average distance between neighboring MePEG chain （0.87 nm） and the thicker fixed aqueous layer thickness （FALT, 5. 16 nm）, PEG5000-PHDCA nanoparticles （80.0 nm ） earned the strongest potency of decreasing uptake by macrophages and prolonging the half-life of rHuTNF-α in rat. Conclusion Within the experimental limits, particle size and MePEG molecular weight had dramatic influence on in vitro macrophage uptake and in vivo long circulating properties of rHuTNF-α-loaded stealth nanoparticles.

关 键 词：肿瘤坏死因子 纳米粒 隐形 长循环 单核吞噬细胞系统 大鼠 

分 类 号：R943.4[医药卫生—药剂学]