Calvo P, Gouritin B, Chacun H, Desmaële D, D'Angelo J, Noel J P, Georgin D, Fattal E, Andreux J P, Couvreur P
Université Paris-Sud XI, UMR CNRS 8612, Physico-Chimie, Pharmacotechnie, Biopharmacie, Châtenay-Malabry, France.
Pharm Res. 2001 Aug;18(8):1157-66. doi: 10.1023/a:1010931127745.
The aim of this study was to evaluate the ability of long-circulating PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue.
Biodistribution profiles and brain concentrations of [14C]-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 of the diffusion of [14C]-sucrose into the brain. The location of fluorescent nanoparticles in the brain was also investigated by epi-fluorescent microscopy.
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.
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.
本研究旨在评估长循环聚乙二醇化氰基丙烯酸酯纳米颗粒扩散进入脑组织的能力。
通过对小鼠和大鼠静脉注射后进行放射性计数，测定[14C]放射性标记的聚乙二醇 - 聚氰基丙烯酸正己酯（PEG - PHDCA）、聚山梨酯80或泊洛沙姆908包被的聚氰基丙烯酸正己酯（PHDCA）纳米颗粒以及未包被的PHDCA纳米颗粒的生物分布情况和脑内浓度。此外，通过体内定量[14C] - 蔗糖向脑内的扩散来评估纳米颗粒给药后血脑屏障（BBB）的完整性。还通过落射荧光显微镜研究了荧光纳米颗粒在脑内的定位。
基于其长循环特性，聚乙二醇化PHDCA纳米颗粒比所有其他测试制剂更能穿透进入脑内。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，在血脑屏障的毛细血管内皮细胞中定位程度较低。这些现象出现时血脑屏障通透性没有任何改变，而聚山梨酯80包被的纳米颗粒部分功效归因于表面活性剂诱导的血脑屏障通透性增加。泊洛沙姆908包被的纳米颗粒未能增加脑内浓度，可能是因为它们无法与细胞相互作用。
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，并强调了为此目的设计合适递送系统的两个要求：a）载体的长循环特性，b）适当的表面特性以允许与血脑屏障内皮细胞相互作用。
