Zhang Xiao-bin, Jin Yi-guang, Xie Ying, Xu Kun, Hou Xin-pu
Department of Physical-pharmacy, School of Pharmacy, Peking University, Beijing 100083, China.
Yao Xue Xue Bao. 2003 Nov;38(11):867-70.
To study the action of RMP-7 and its derivative on transporting liposome across the blood brain barrier (BBB) into the brain.
RMP-7 and DSPE-PEG-NHS [[1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-n-[poly (ethylene-glycol)]-hydroxy succinamide]] were conjugated together in mild condition and MALDI-TOF-MS (Matrix-Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry) was used to determine their molecular ratio. An in vitro BBB model was established and used to determine in vitro bioactivity of RMP-7 and its derivative. The fluorescence of brain slices and the Evens Blue (EB) concentration in the brain, liver, spleen, lung and kidney of each group were used to evaluate the in vivo bioactivity of RMP-7 and its derivative on transporting liposome across the BBB.
The average molecular weight (MW) of the reaction product was 4,900, while those of DSPE-PEG-NHS and RMP-7 were 3,224 and 1,098. The results demonstrated that RMP-7 was conjugated to DSPE-PEG-NHS at the molecular ratio of 1:1, so the product was DSPE-PEG-RMP-7. RMP-7 and DSPE-PEG-RMP-7 was shown to improve the transporting of peralcohol enzyme across the in vitro BBB model 2-3 times higher than the peralcohol enzyme only. DSPE-PEG-RMP-7 could facilitate the transporting of EB into brain more easily than RMP-7.
Both RMP-7 and DSPE-PEG-RMP-7 could facilitate the transporting of liposome across the BBB, especially DSPE-PEG-RMP-7.
研究RMP - 7及其衍生物对脂质体跨越血脑屏障（BBB）进入脑内的作用。
在温和条件下将RMP - 7与DSPE - PEG - NHS [[1,2 - 二油酰 - sn - 甘油 - 3 - 磷酸乙醇胺 - n - [聚（乙二醇）] - 羟基琥珀酰胺]]偶联在一起，并用基质辅助激光解吸电离飞行时间质谱（MALDI - TOF - MS）测定它们的分子比例。建立体外血脑屏障模型并用于测定RMP - 7及其衍生物的体外生物活性。每组脑切片的荧光以及脑、肝、脾、肺和肾中伊文思蓝（EB）的浓度用于评估RMP - 7及其衍生物在脂质体跨越血脑屏障转运方面的体内生物活性。
反应产物的平均分子量（MW）为4900，而DSPE - PEG - NHS和RMP - 7的平均分子量分别为3224和1098。结果表明RMP - 7与DSPE - PEG - NHS以1:1的分子比例偶联，所以产物为DSPE - PEG - RMP - 7。RMP - 7和DSPE - PEG - RMP - 7显示出能使过醇酶跨越体外血脑屏障模型的转运能力比仅过醇酶提高2 - 3倍。DSPE - PEG - RMP - 7比RMP - 7能更轻易地促进EB进入脑内。
RMP - 7和DSPE - PEG - RMP - 7都能促进脂质体跨越血脑屏障，尤其是DSPE - PEG - RMP - 7。
