Drug transport to brain with targeted nanoparticles.
Drug transport to brain with targeted nanoparticles.
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DOI：
10.1602/neurorx.2.1.108
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发表时间：
2005-01-01
期刊：
影响因子：
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通讯作者：
Olivier, Jean-Christophe
中科院分区：
文献类型：
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作者：
Olivier, Jean-Christophe
纳米颗粒药物载体由尺寸范围为10 - 1000 nm（通常为50-300 nm）的固体生物可降解颗粒组成。它们不能通过血脑屏障（BBB）自由扩散，需要受体介导的转运通过脑毛细血管内皮细胞将其内容物递送到脑实质中。聚山梨醇酯80涂层的聚氰基丙烯酸正丁酯纳米颗粒可以通过一种仍有争议的机制将药物输送到大脑。尽管有趣的结果，这些纳米粒子有局限性，在这次审查中讨论，可能会妨碍，或至少限制，其潜在的临床应用。由甲氧基聚（乙二醇）-聚丙交酯或聚（丙交酯-共-乙交酯）（mPEG-PLA/PLGA）制成的长循环纳米粒具有良好的安全性，并提供药物缓释。功能化PEG-PLA的可用性允许通过细胞表面配体的缀合来制备靶向特异性纳米颗粒。使用BBB转胞吞受体的拟肽抗体，现在可以合成脑靶向聚乙二醇化免疫纳米颗粒，其应该使得将截留的活性物质递送到脑实质中而不诱导BBB通透性改变成为可能。本文介绍了它们的一般性质（结构，负载能力，药代动力学）和目前可用的免疫纳米颗粒的制备方法。
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.