Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.
J Drug Target. 2010 Aug;18(7):536-49. doi: 10.3109/10611861003587235.
New glycosyl derivative of cholesterol was synthesized as a material for preparing novel liposome to overcome the ineffective delivery of normal drug formulations to brain by targeting the (glucose transporters) GLUTs on the BBB. Coumarin-6 was used as fluorescent probe. The results have shown that the cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose-mediated brain targeting liposome containing coumarin-6 was less than that of conventional liposome. The BBB model in vitro was established by coculturing of BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing the BBB. The transendothelial ability was confirmed strengthen alone with the amount of the new glycosyl derivative of cholesterol used in liposome. After i.v. administration of LIP, control liposome (CLP), and GLP-4, the AUC(0-t) of coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times higher than that of CLP. The C(max) of CLP-4 was 1.43 times higher than that of LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and distribution in mice were also investigated to show that this novel brain targeting drug delivery system was promising.
新型胆固醇糖基衍生物被合成作为一种制备新型脂质体的材料，以克服通过靶向 BBB 上的（葡萄糖转运蛋白）GLUTs 将普通药物制剂有效递送到大脑的问题。香豆素-6 被用作荧光探针。结果表明，含有香豆素-6 的葡萄糖介导的脑靶向脂质体对脑毛细血管内皮细胞 (BCEC) 的细胞毒性小于常规脂质体。通过共培养大鼠 BCEC 和星形胶质细胞 (AC) 建立体外 BBB 模型，以测试穿过 BBB 的跨内皮能力。随着脂质体中新型糖基胆固醇衍生物的用量增加，证实了跨内皮能力的增强。静脉注射 LIP、对照脂质体 (CLP) 和 GLP-4 后，GLP-4 的香豆素-6 的 AUC(0-t) 是 LIP 的 2.85 倍，是 CLP 的 3.33 倍。CLP-4 的 C(max) 是 LIP 的 1.43 倍，是 CLP 的 3.10 倍。在小鼠中的药代动力学和分布也进行了研究，表明这种新型的脑靶向药物递送系统具有很大的潜力。
