Department of Chemical Engineering, National Chung Cheng University, Taiwan, Republic of China.
Int J Pharm. 2011 Sep 15;416(1):365-75. doi: 10.1016/j.ijpharm.2011.06.037. Epub 2011 Jun 28.
Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) with surface poly-(γ-glutamic acid) (γ-PGA) were applied to enhance the transport of saquinavir (SQV) across the blood-brain barrier (BBB). PLGA NPs encapsulated SQV and grafted with γ-PGA to form drug carriers (γ-PGA/SQV-PLGA NPs) for crossing through a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated with human astrocytes. The results revealed that a lower molecular weight of γ-PGA yielded a higher grafting efficiency of γ-PGA on PLGA NPs. In addition, γ-PGA with a low molecular weight accelerated the dissolution of SQV from γ-PGA/SQV-PLGA NPs. A higher grafting efficiency (more didecyl dimethylammonium bromide) and a lower molecular weight of γ-PGA increased the permeability of SQV across the BBB, in general. When the grafting efficiency was 85.2% at 6kDa of γ-PGA, γ-PGA/SQV-PLGA NPs reached about 6 times the permeability of free SQV (the maximal permeability). γ-PGA could also promote the endocytosis of NPs and expression of ornithine decarboxylase by HBMECs. γ-PGA/SQV-PLGA NPs are efficacious nanoparticulate carriers in delivering antiretroviral drug across the BBB.
聚（丙交酯-共-乙交酯）（PLGA）纳米粒子（NPs）表面接枝聚-γ-谷氨酸（γ-PGA）可增强 saquinavir（SQV）通过血脑屏障（BBB）的转运。PLGA NPs 包载 SQV 并接枝 γ-PGA 形成药物载体（γ-PGA/SQV-PLGA NPs），以穿过受星形胶质细胞调控的单层人脑微血管内皮细胞（HBMECs）。结果表明，较低分子量的 γ-PGA 可获得更高的 PLGA NPs 接枝效率。此外，低分子量的 γ-PGA 加速了 SQV 从 γ-PGA/SQV-PLGA NPs 中的溶解。较高的接枝效率（更多的双十烷基二甲基溴化铵）和较低分子量的 γ-PGA 普遍增加了 SQV 通过 BBB 的通透性。当 γ-PGA 分子量为 6kDa 时接枝效率为 85.2%时，γ-PGA/SQV-PLGA NPs 的通透性达到游离 SQV（最大通透性）的约 6 倍。γ-PGA 还可促进 NPs 的内吞作用和 HBMECs 中鸟氨酸脱羧酶的表达。γ-PGA/SQV-PLGA NPs 是一种有效的纳米载体，可将抗逆转录病毒药物递送至 BBB。
