Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India.
Drug Dev Ind Pharm. 2020 Mar;46(3):471-483. doi: 10.1080/03639045.2020.1730396. Epub 2020 Feb 27.
The objective of the research undertaken was to develop the Riluzole (RIZ) nanoparticles drug delivery system using Transferrin (Tf) as a ligand in the brain. RIZ-loaded chitosan nanoparticles and RIZ-Tf chitosan (CS) nanoparticles (RIZ CSNPs and RIZ-Tf CSNPs) were formulated and compared for particles size, size distribution, encapsulation efficiency, and surface morphology, respectively. The drug release, permeation, pharmacokinetic, biochemical, and pharmacodynamic experiments were done to assess the improvement in fate and efficacy of RIZ. The size of optimized RIZ CSNPs was found to be 173.6 ± 2.23 nm and polydispersity index (PDI) of 0.264 ± 0.002 while that of RIZ-Tf CSNPs was 207 ± 2.49 nm and 0.406 ± 0.002. release was found to be 86.15 ± 7.316% and 91.1 ± 5.836%, respectively, while permeability coefficient was found to be 4 × 10 and 4.2 × 10cm/s for RIZ CSNPs and RIZ-Tf CSNPs. The biochemical analysis studies revealed that oxidative stress was significantly decreased in case of RIZ CSNPs and RIZ-Tf CSNPs ( < 0.01) treated groups. The antianxiety effect and the memory restoration were evident in pharmacodynamic studies ( < 0.05) of the prepared formulations. The results of pharmacokinetic studies demonstrated the remarkable brain delivery of RIZ-Tf CSNPs through intranasal route as compared to the RIZ solution.
本研究旨在开发一种将利鲁唑(RIZ)制成纳米药物输送系统,并使用转铁蛋白(Tf)作为脑内配体。分别对载利鲁唑壳聚糖纳米粒(RIZ-loaded chitosan nanoparticles,RIZ-CSNPs)和载利鲁唑-Tf 壳聚糖(RIZ-Tf chitosan,RIZ-Tf CSNPs)纳米粒进行了制剂研究,比较了其粒径、粒径分布、包封率和表面形态。分别进行了药物释放、渗透、药代动力学、生化和药效学实验,以评估 RIZ 命运和疗效的改善。优化后的 RIZ-CSNPs 的粒径为 173.6±2.23nm,多分散指数(polydispersity index,PDI)为 0.264±0.002;而 RIZ-Tf CSNPs 的粒径为 207±2.49nm,PDI 为 0.406±0.002。结果显示,RIZ-CSNPs 和 RIZ-Tf CSNPs 的释放率分别为 86.15±7.316%和 91.1±5.836%,渗透系数分别为 4×10-4和 4.2×10-4cm/s。生化分析研究表明,RIZ-CSNPs 和 RIZ-Tf CSNPs 处理组的氧化应激显著降低(<0.01)。药效学研究表明,RIZ-CSNPs 和 RIZ-Tf CSNPs 具有明显的抗焦虑作用和记忆恢复作用(<0.05)。药代动力学研究结果表明,与 RIZ 溶液相比,RIZ-Tf CSNPs 经鼻内给药具有显著的脑内递药效果。