Olivier Jean-Christophe
Faculty of Medicine and Pharmacy, University of Poitiers, 86000 Poitiers, France.
NeuroRx. 2005 Jan;2(1):108-19. doi: 10.1602/neurorx.2.1.108.
Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50-300 nm generally). They cannot freely diffuse through the blood-brain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)- polylactide or poly(lactide-co-glycolide) (mPEG-PLA/PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.
纳米颗粒药物载体由尺寸范围为10至1000纳米（通常为50 - 300纳米）的固体可生物降解颗粒组成。它们不能自由扩散通过血脑屏障（BBB），需要通过受体介导的转运穿过脑毛细血管内皮细胞，将其内含物输送到脑实质中。聚山梨酯80包被的聚氰基丙烯酸丁酯纳米颗粒可以通过一种仍存在争议的机制将药物输送到大脑。尽管有有趣的结果，但这些纳米颗粒存在局限性，本综述将对此进行讨论，这些局限性可能会排除或至少限制它们的潜在临床应用。由甲氧基聚（乙二醇） - 聚丙交酯或聚（丙交酯 - 共 - 乙交酯）（mPEG - PLA/PLGA）制成的长循环纳米颗粒具有良好的安全性，并能实现药物的持续释放。功能化PEG - PLA的可用性使得通过细胞表面配体的缀合制备靶向特异性纳米颗粒成为可能。利用拟肽抗体靶向血脑屏障转胞吞受体，现在可以合成脑靶向聚乙二醇化免疫纳米颗粒，这应该能够在不引起血脑屏障通透性改变的情况下，将包封的活性物质输送到脑实质中。本综述介绍了它们的一般性质（结构、载药量、药代动力学）以及目前可用的免疫纳米颗粒制备方法。
