RMP-7及其衍生物对脂质体跨血脑屏障作用的影响

目的研究RMP-7及其衍生物对脂质体跨血脑屏障的促进作用。方法测定RMP-7与DSPE-PEG-NHS偶联的物质的量比；用血脑屏障的体外模型验证其生物活性；观察脑组织切片中伊文思蓝的荧光位置和强度，测定脑组织中伊文思蓝的浓度。结果RMP-7与DSPE-PEG-NHS偶联物质的量比为1∶1；RMP-7和DSPE-PEG-RMP-7能使过氧化合物酶跨血脑屏障体外模型的转运速率增加2～3倍，修饰脂质体后能使所包封的伊文思蓝在脑中的浓度增加。结论RMP-7与DSPE-PEG-RMP-7对脂质体跨血脑屏障均有促进作用，且后者效果更好。

Effect of RMP-7 and its derivatives on the transportation of liposome into the brain

AIM: To study the action of RMP-7 and its derivative on transporting liposome across the blood brain barrier (BBB) into the brain. METHODS: 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. RESULTS: 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. CONCLUSION: Both RMP-7 and DSPE-PEG-RMP-7 could facilitate the transporting of liposome across the BBB, especially DSPE-PEG-RMP-7.