Cationic charge-dependent hepatic delivery of amidated serum albumin
Cationic charge-dependent hepatic delivery of amidated serum albumin
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DOI：
10.1016/j.jconrel.2004.11.006
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发表时间：
2005-02-16
影响因子：
10.8
通讯作者：
Hashida, M
中科院分区：
文献类型：
--
作者：
Ma, SF;Nishikawa, M;Hashida, M
为了获得胺化牛血清白蛋白(BSA)的物理化学性质与其组织分布特征之间的定量关系，以开发蛋白质靶向传递，将BSA与六甲二胺(HMD)或乙二胺(ED)进行酰胺化，得到阳离子BSA。用光谱学和电泳法检测了它们的结构变化，并研究了它们在小鼠体内的组织分布。圆二色谱(CD)和荧光测量表明，随着NH2基团数目的增加，光谱发生了变化。毛细管电泳法显示，游离性与NH2基团数目的增加呈线性关系。(111)阳离子BSA能迅速被肝脏摄取，但HMD-BSA的摄取速度比ED-BSA快，具有相同数量的游离NH2基团，这表明具有较长羧基侧链的二胺试剂具有更高的肝脏靶向性。两种衍生物的肝摄取清晰度(CLliver)随着向阳极的电泳率(p，p)的降低而显著增加，并在低电泳率时达到平台期。电泳迁移率是酰胺化程度的一个合适的指标，这与肝脏摄取清除率密切相关。迁移率和清除度之间的相关性表明，低程度的酰胺化足以有效地靶向蛋白质的肝脏。(C)2004爱思唯尔B.V保留所有权利。
To obtain a quantitative correlation between the physicochemical properties of amidated bovine serum albumin (BSA) and their tissue distribution characteristics for the development of targeted delivery of proteins, BSA was amidated with hexamethylenediamine (HMD) or ethylenediamine (ED) to obtain cationized BSAs. Their structural changes were examined by spectroscopic and electrophoretic techniques then their tissue distribution was studied in mice. Circular dichroism (CD) and fluorescence measurements showed that spectroscopic changes occurred as the number of free NH2 groups increased. Capillary electrophoresis revealed a linear relationship between the mobility and the increased number of free NH2 groups. (111)Incationized BSAs were rapidly taken up by liver, but HMD-BSA showed a faster uptake than ED-BSA with a similar number of free NH2 groups, suggesting that the diamine reagent with a longer carboxyl side chain results in more efficient hepatic targeting. The hepatic uptake clearance (CLliver) of both derivatives increased significantly with a decrease in electrophoretic mobility (p,p) towards the anode and reached a plateau at low electrophoretic mobility. The electrophoretic mobility is an appropriate indicator of the degree of amidation, which was closely correlated with the hepatic uptake clearance. The correlation between the mobility and the clearance shows that a low degree of amidation is sufficient for efficient hepatic targeting of proteins. (C) 2004 Elsevier B.V All rights reserved.