Cationic albumin conjugated pegylated nanoparticle with its transcytosis ability and little toxicity against blood-brain barrier
Cationic albumin conjugated pegylated nanoparticle with its transcytosis ability and little toxicity against blood-brain barrier
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DOI：
10.1016/j.ijpharm.2005.01.043
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发表时间：
2005-05-13
影响因子：
5.8
通讯作者：
Jiang, XG
中科院分区：
文献类型：
--
作者：
Lu, W;Tan, YZ;Jiang, XG
我们新开发的药物递送载体，阳离子牛血清白蛋白（CBSA）共轭聚乙二醇-聚乳酸（PEG-PLA）纳米粒子（CBSA-NP），设计用于脑药物递送。CBSA作为脑特异性靶向剂，与聚乙二醇（PEG）远端的马来酰亚胺官能团共价结合，包围纳米颗粒。为了评价其对血脑屏障（BBB）的转胞吞作用和对BBB内皮紧密连接的毒性，我们探索了一种将脑毛细血管内皮细胞（BCECs）置于细胞培养插入物的微孔膜的顶部，星形胶质细胞置于底部的共培养方法。测定C-14标记蔗糖的渗透性。对于CBSA-NP转胞吞作用研究，将亲脂性荧光探针6-香豆素掺入纳米颗粒中。计算CBSA-NP的体外血脑屏障通透性，并与天然牛血清白蛋白（BSA）缀合的聚乙二醇化纳米颗粒（BSA-NP）进行比较。作为共培养模型，跨内皮电阻高达313 +/- 23 Ω cm（2）。扫描电镜和透射电镜可见共培养的BCECs间紧密连接。与200 μ g/ml CBSA-NP的出现相比，C-14标记的蔗糖的渗透性未改变，证明CBSA-NP不影响BBB的完整性;内皮紧密连接。CBSA-NP对BCEC也显示出很小的毒性。CBSA-NP的渗透性是BSA-NP的7.76倍，但过量的游离CBSA可抑制转胞吞作用。得出的结论是，CBSA-NP优先穿过BBB，毒性很小，这为将治疗药物递送到中枢神经系统提供了可能性。(c)2005 Elsevier B. V.保留所有权利。
Our newly developed drug delivery carrier, cationic bovine serum albumin (CBSA) conjugated with poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA-NP), was designed for brain drug delivery. CBSA, as a brain specific targetor, was covalently conjugated with the maleimide function group at the distal of poly(ethyleneglycol) (PEG) surrounding the nanoparticles. To evaluate its blood-brain barrier (BBB) transcytosis and toxicity against the BBB endothelial tight junction, we have explored a method of coculture with brain capillary endothelial cells (BCECs) on the top of micro-porous membrane of cell culture insert and astrocytes on the bottom side. The permeability of C-14-labeled Sucrose was determined. For the CBSA-NP transcytosis study, a lipophilic fluorescent probe, 6-coumarin, was incorporated into nanoparticles. The BBB permeability of CBSA-NP in vitro was calculated and compared with native bovine serum albumin (BSA) conjugated pegylated nanoparticles (BSA-NP). As the coculture model, the transendothelial electrical resistance reached up to 313 +/- 23 Omega cm(2). The tight junction between BCECs in the coculture could be visualized by scanning electron microscopy and transmission electron microscopy. The unchanged permeability of C-14-labeled sucrose comparing to that in the appearance of 200 mu g/ml of CBSA-NP proved that CBSA-NP did not impact the integrity of BBB; endothelial tight junctions. CBSA-NP also showed little toxicity against BCECs. The permeability of CBSA-NP was about 7.76 times higher than that of BSA-NP, while the transcytosis was inhibited in the excess of free CBSA. It was concluded that CBSA-NP preferentially transported across BBB with little toxicity, which offered the possibility to deliver therapeutic agents to CNS. (c) 2005 Elsevier B.V. All rights reserved.