Development and Evaluation of Riluzole Loaded PLGA Nanoparticles for Improved Permeability across BBB

Abstract

Blood-brain barrier is a physiological barrier that prevents drugs from reaching the brain or being bioavailable for treating brain disorders. Degenerative diseases like amyotrophic lateral sclerosis (ALS) seriously impact our daily lives. The Food and Drug Administration (FDA) approved this drug to treat ALS as a chemical derivative of 2-amino-6 [tri-fluoro-methoxy] benzo-thiazole. In order to improve the drug’s therapeutic efficacy, poly-(lactic-co-glycolic acid) nanoparticles (PLGA) were loaded with riluzole and deposited using emulsifying solvent deposition. A design expert software program was used to optimize formulation parameters, including polymer concentration, surfactant concentration, and stirring speed, based on the particle size, zeta potential, and entrapment efficiency responses. Three formulations were taken forward for further study based on the results of 20 trials. Compared to differential scanning calorimetry and fourier transform infrared spectroscopy (FTIR) studies performed beforehand, there were no significant interactions between RZL and the excipients. Nanoparticles prepared with scanning electron microscopy had a smooth surface and a spherical shape. The particle size distribution ranged from 184 ± 74 nm to a maximum of 204.5 ± 71. As a consequence, the particle size distribution is relatively narrow, with lower polymer concentrations, and is ideal for drug delivery. A range of-17.3 to-18.2mV was found for the zeta potential of the nanoparticles. The encapsulation efficiency ranged from 42.61 ± 3.61 to 60.02 ± 1.94%, forming 1:1 to 1:4 drug: Polymer ratios, respectively. Over a period of 22 to 26 hours, the RLZ was continuously released from the nanoparticles. A loading dose may be built by 24% of the drug being released within 3 hours of administration.