The objective of this study was to formulate and investigate the neuropharmacokinetics and pharmacodynamics of rivastigmine (Riv) loaded methoxy poly(ethylene glycol)-co-poly(ε-caprolactone) (MPEG-PCL) nanoparticles (Riv-NPs) in rats after IV administration. The MPEG-PCL was synthesized via ring-opening polymerization of ε-caprolactone by MPEG and used to prepare Riv-NPs by the nanoprecipitation method. Response surface D-optimal design was applied to optimize Riv-NPs drug delivery system. The optimized formulation showed a particle size (PS) of 98.5 ± 2.1 nm, drug loading (DL) of 19.2 ± 1.1%, and sustained release behavior of the drug. Moreover, the optimized Riv-NPs were characterized by AFM and DSC analyses. A simple and sensitive HPLC-DAD method for bioanalysis was developed and successfully applied to the pharmacokinetic study. The neuropharmacokinetic study in rats indicated that the integration plot was linear, and the brain uptake clearance of the drug-loaded in MPEG-PCL NPs was significantly higher than the free drug. Furthermore, results of pharmacodynamic studies using the Morris water maze test demonstrated faster regain of memory loss with Riv-NPs when compared to the free drug solution. The results revealed that the mentioned biodegradable nanoparticle holds promise as a suitable drug carrier for brain drug delivery.

中文翻译：

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利伐斯的明负载的甲氧基聚（乙二醇）-共聚（ε-己内酯）纳米粒子的制备，优化和评价。

这项研究的目的是制定和研究静脉注射利伐斯明（Riv）负载甲氧基聚（乙二醇）-共聚（ε-己内酯）（MPEG-PCL）纳米颗粒（Riv-NPs）的神经药代动力学和药效学行政。MPEG-ε-己内酯通过MPEG的开环聚合反应合成了MPEG-PCL，并通过纳米沉淀法制备了Riv-NP。响应面D最优设计用于优化Riv-NPs药物递送系统。优化的制剂显示出98.5±2.1 nm的粒径（PS），19.2±1.1％的载药量（DL）和药物的缓释性能。此外，通过AFM和DSC分析表征了优化的Riv-NP。开发了一种简单而灵敏的HPLC-DAD生物分析方法，并将其成功地用于药代动力学研究。在大鼠中进行的神经药代动力学研究表明，积分图是线性的，并且以MPEG-PCL NPs负载的药物的脑部摄取清除率明显高于游离药物。此外，使用莫里斯水迷宫测试的药效学研究结果表明，与游离药物溶液相比，Riv-NPs可以更快地恢复记忆丧失。结果表明，所述可生物降解的纳米颗粒有望作为脑药物递送的合适药物载体。使用莫里斯水迷宫测试进行药效学研究的结果表明，与游离药物溶液相比，Riv-NPs可以更快地恢复记忆丧失。结果表明，所述可生物降解的纳米颗粒有望作为脑药物递送的合适药物载体。使用莫里斯水迷宫测试进行药效学研究的结果表明，与游离药物溶液相比，Riv-NPs可以更快地恢复记忆丧失。结果表明，所述可生物降解的纳米颗粒有望作为脑药物递送的合适药物载体。