Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery
Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery
复制标题
DOI：
10.1023/a:1010931127745
复制
发表时间：
2001-08-01
影响因子：
3.7
通讯作者：
Couvreur, P
中科院分区：
文献类型：
--
作者：
Calvo, P;Gouritin, B;Couvreur, P
目的.本研究的目的是评估长循环聚乙二醇化氰基丙烯酸酯纳米颗粒扩散到脑组织中的能力。小鼠和大鼠静脉给药后，通过放射性计数测定[C-14]-放射性标记的PEG-PHDCA、聚山梨酯80或泊洛沙胺908包被的PHDCA纳米颗粒和未包被的PHDCA纳米颗粒的生物分布特征和脑浓度。此外，通过体内定量或[C-14]-蔗糖向脑中的扩散来评价纳米颗粒施用后血脑屏障（BBB）的完整性。荧光纳米颗粒在脑中的位置也通过落射荧光显微镜进行了研究。基于其长循环特性，PEG化PHDCA纳米颗粒比所有其他测试制剂更大程度地渗透到大脑中。颗粒定位于脉络丛的室管膜细胞，软脑膜和脑室的上皮细胞，并在较低程度上在血脑屏障的毛细血管内皮细胞。这些现象的发生没有任何修改的血脑屏障通透性，而聚山梨酯80包被的纳米粒子欠，部分，他们的疗效，以血脑屏障透化诱导的表面活性剂。泊洛沙胺908涂层纳米粒未能增加脑浓度可能是因为它们不能与细胞相互作用。本研究提出聚乙二醇化聚（氰基丙烯酸酯）纳米颗粒作为一种新的脑递送系统，并强调了设计用于此目的的适当递送系统的两个要求：a）载体的长循环特性，和B）适当的表面特性，以允许与BB B内皮细胞相互作用，
Purpose. The aim of this study was to evaluate the ability of long-circulating PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue.Methods. Biodistribution profiles and brain concentrations of [C-14]-radiolabeled PEG-PHDCA, polysorbate 80 or poloxamine 908-coated PHDCA nanoparticles, and uncoated PHDCA nanoparticles were determined by radioactivity counting after intravenous administration in mice and rats. In addition, the integrity of the blood-brain barrier (BBB) after nanoparticles administration was evaluated by in vivo quantification or the diffusion of [C-14]-sucrose into the brain. The location of fluorescent nanoparticles in the brain was also investigated by epi-fluorescent microscopy.Results. Based on their long-circulating characteristics, PEGylated PHDCA nanoparticles penetrated into the brain to a larger extent than all the other tested formulations. Particles were localized in the ependymal cells of the choroid plexuses, in the epithelial cells of pia mater and ventricles, and to a lower extent in the capillary endothelial cells of BBB. These phenomena occurred without any modification of BBB permeability whereas polysorbate 80-coated nanoparticles owed, in part, their efficacy to BBB permeabilization induced by the surfactant. Poloxamine 908-coated nanoparticles failed to increase brain concentration probably because of their inability to interact with cells.Conclusions. This study proposes PEGylated poly (cyanoacrylate) nanoparticles as a new brain delivery system and highlights two requirements to design adequate delivery systems for such a purpose: a) long-circulating properties of the carrier, and b) appropriate surface characteristics to allow interactions with BBB endothelial cells,