Riluzole-loaded nanoparticles to alleviate the symptoms of neurological disorders by attenuating oxidative stress

Abstract

<b>Purpose:</b> 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.<b>Method:</b> 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 <i>in vitro</i> drug release, permeation, pharmacokinetic, biochemical, and pharmacodynamic experiments were done to assess the improvement in <i>in vivo</i> fate and efficacy of RIZ.<b>Results:</b> 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. <i>In vitro</i> release was found to be 86.15 ± 7.316% and 91.1 ± 5.836%, respectively, while permeability coefficient was found to be 4 × 10^-2 and 4.2 × 10^-2cm/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 (<i>p</i> < 0.01) treated groups. The antianxiety effect and the memory restoration were evident in pharmacodynamic studies (<i>p</i> < 0.05) of the prepared formulations.<b>Conclusion:</b> The results of pharmacokinetic studies demonstrated the remarkable brain delivery of RIZ-Tf CSNPs through intranasal route as compared to the RIZ solution.