Fang Chao, Shi Bin, Hong Ming-huang, Pei Yuan-ying, Chen Hong-zhuan
Department of Pharmacology, College of Basic Medical Sciences, Shanghai Jiao Tong University, China.
Yao Xue Xue Bao. 2006 Apr;41(4):305-12.
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-alpha (rHuTNF-alpha)-loaded stealth nanoparticles in rats.
Three sizes (approximately 80, 70 and 240 nm) of poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles loading rHuTNF-alpha 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.
The uptake by macrophages decreased and the half-life of rHuTNF-alpha 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), PEG5,000-PHDCA nanoparticles (80.0 nm) earned the strongest potency of decreasing uptake by macrophages and prolonging the half-life of rHuTNF-alpha in rat.
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-alpha-loaded stealth nanoparticles.
研究粒径和甲氧基聚乙二醇（MePEG）分子量对载重组人肿瘤坏死因子-α（rHuTNF-α）隐形纳米粒在大鼠体内的体外巨噬细胞摄取及体内长循环的影响。
采用复乳法，在不同的MePEG分子量（Mr 2000、5000、10000）下制备三种粒径（约80、70和240 nm）的载rHuTNF-α的聚（甲氧基聚乙二醇氰基丙烯酸酯-共-正十六烷基氰基丙烯酸酯）（PEG-PHDCA）纳米粒。检测并比较其在大鼠体内的体外巨噬细胞摄取及体内长循环特性。
随着MePEG分子量的增加或粒径的减小，巨噬细胞摄取量降低，rHuTNF-α在大鼠体内的半衰期延长。粒径和MePEG分子量与体外巨噬细胞摄取及体内长循环特性之间的线性关系良好。PEG5000-PHDCA纳米粒（80.0 nm）具有最高的MePEG表面密度（1.32 nm-2）、相邻MePEG链之间最短的平均距离（0.87 nm）和较厚的固定水层厚度（FALT，5.16 nm），其降低巨噬细胞摄取和延长rHuTNF-α在大鼠体内半衰期的能力最强。
在实验范围内，粒径和MePEG分子量对载rHuTNF-α隐形纳米粒的体外巨噬细胞摄取及体内长循环特性有显著影响。
