赛罗帕提及其衍生物对两性霉素B脂质体跨大鼠血脑屏障的作用

Effects of Cereport and its derivative on the transporting of amphotericin B liposome across the blood brain barrier of rats

目的 制备赛罗帕提 (Cereport ,又名RMP 7)的衍生物并用于修饰两性霉素B脂质体 ,以提高两性霉素B进入脑组织的能力。方法 用改良薄膜超声法制备了两性霉素B脂质体 ,将RMP 7与DSPE PEG NHS{ 1,2 dioleoyl sn glycero 3 phospho ethanolamine n [poly (ethylenegly col) ] hydroxysuccinamide ,PEGM 340 0 }连接后用基质辅助激光解吸附飞行时间质谱法 (Ma trix AssistedLaserDesorption IonizationTime of FlightMassSpectrometry ,MALDI TOF MS)测定产物的分子量以计算二者偶联的比例 ,然后将所得产物插入两性霉素B脂质体的表面 ,测定脂质体的粒径 ,经股静脉给药后用高效液相色谱法测定大鼠的脑、肝、脾、肺和肾等脏器中两性霉素B的浓度。结果 两性霉素B脂质体的包封率为 (93.5 1± 1.5 6 ) % ,平均粒径为 (5 5 .7± 7.1)nm。RMP 7与DSPE PEG为 1∶1连接 ,在脂质体表面用所得衍生物修饰后 ,能显著提高两性霉素B在大鼠脑组织中的浓度 ,而不影响药物在其它脏器中的分布。结论 RMP 7和其衍生物DSPE PEG RMP 7能提高两性霉素B脂质体跨过血脑屏障进入脑组织的能力。

OBJECTIVE: To improve the transporting of amphotericin B (AmB) across the blood brain barrier (BBB) into the brain. RMP-7 was conjugated to DSPE-PEG and the product was used to modify the amphotericin B liposome. METHODS: The amphotericin B liposome was prepared by the modified film-sonication method and the diameter distribution was determined by the photo correlation spectroscopy. RMP-7 was conjugated to DSPE-PEG-NHS at mild condition and the product was detected by MALDI-TOF-MS to determine the reaction ratio between RMP-7 and DSPE-PEG-NHS. The product was used to modify the amphotericin B liposome and then the amphotericin B concentrations in the brain, liver, spleen, lung and kidney of rats were respectively determined by the HPLC method. RESULTS: The encapsulation percentage of amphotericin B liposome was (93.51 ± 1.56) %. The average diameter of amphotericin B liposome was (55.7 ± 7.1) nm. The RMT-7 was conjugated to DSPE-PEG-NHS at the molecular ratio of 1:1. The product was used to modify the amphotericin B liposome and the amphotericin B concentration in the brain was improved several times higher compared with conventional amphotericin B liposome, while the amphotericin B concentration in other tissues were not changed. CONCLUSION: RMP-7 and its derivative (DSPE-PEG-RMP-7) could improve the transporting of amphotericin B liposome across the blood brain barrier into the brain, especially the derivative.