High-efficacy site-directed drug delivery system using sialyl-Lewis X conjugated liposome
High-efficacy site-directed drug delivery system using sialyl-Lewis X conjugated liposome
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DOI：
10.1016/j.exer.2007.10.004
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Tano, Yasuo
中科院分区：
文献类型：
--
作者：
Hashida, Noriyasu;Ohguro, Nobuyuki;Tano, Yasuo
本研究的目的是利用小鼠实验性自身免疫性葡萄膜视网膜炎(EAU)模型，评价新开发的唾液酸-刘易斯-X结合脂质体(SLE(X)L)作为体内活化内皮细胞的定点递送系统。用该脂质体制备了4种纳米粒：异硫氰酸荧光素标记的系统性红斑狼疮(X)、L(F-SLE(X)L)及其载体(F-L)、含地塞米松的SLE(X)L(d-SLE(X)L)和不含SLE(X)的地塞米松脂质体(d-L)。首先，在Eau小鼠体内注射F-SLE(X)L或F-L后，用共聚焦激光扫描显微镜观察FITC的连续组织积聚。其次，在EAU小鼠静脉注射F-SLE(X)L之前，用抗E-选择素抗体作为阻断抗体，观察该抗体对F-SLE(X)L蓄积的抑制作用。第三，用放射免疫法测定d-SLE(X)L(总地塞米松2 mg)或游离地塞米松溶液(1 Mg)注射后各脏器中地塞米松的浓度。仅在F-SLE(X)L治疗的EAU小鼠中观察到FITC的聚集。F-SLE(X)L在激活的内皮细胞上5分钟内蓄积，用抗E-选择素抗体抑制其蓄积。FITC的颜色依次分散到整个视网膜。D-SLE(X)L对发炎的眼睛显示出选择性靶向，其中地塞米松的浓度大约是1毫克游离地塞米松的两倍。系统性红斑狼疮(X)L在体内可作为一种高效的定位系统。利用红斑狼疮(X)L作为给药载体，在炎症性疾病中应能获得实质性的药理作用和最小的副作用。(C)2007爱思唯尔有限公司。保留所有权利。
The aim of this study was to evaluate the new developed sialyl-Lewis X conjugated liposome (sLe(X)L) as a site-directed delivery system to activated endothelial cells in vivo using a murine experimental autoimmune uveoretinitis (EAU) model. Four types of nanoparticles were prepared using this liposome: fluorescein isothiocyanate (FITC) labeled sLe(X)L (F-sLe(X)L) and its vehicle (F-L), sLe(X)L containing dexamethasone (d-sLe(X)L) and liposome without sLe(X) containing dexamethasone (d-L). First, after a bolus injection of F-sLe(X)L or F-L into EAU mice, sequential tissue accumulation of FITC was examined by confocal laser scanning microscopy. Second, anti-E-selectin antibody, as a blocking antibody, was given intravenously to EAU mice prior to the injection of F-sLe(X)L in order to investigate the effect of the antibody on inhibition of the accumulation of F-sLe(X)L. Third, concentration of dexamethasone in several organs after the injection of d-sLe(X)L (total dexamethasone 2 mu g) or free dexamethasone solution (1 mg) was measured by radioimmunoassay. Accumulation of FITC was only observed in F-sLe(X)L treated EAU mice. F-sLe(X)L accumulated on the activated endothelial cells within 5 min; accumulation then was inhibited using anti-E-selectin antibody. The FITC color was dispersed sequentially to the entire retina. d-sLe(X)L showed selective targeting to the inflamed eye, where an approximately two-fold higher dexamethasone concentration was achieved compared with 1 mg free dexamethasone. sLe(X)L can be a highly efficacious site-directed system in vivo. Using sLe(X)L as a vehicle for drug delivery, substantial pharmacologic effects with minimum side effects in inflammatory diseases should be achieved. (C) 2007 Elsevier Ltd. All rights reserved.