Optimization and characterization of lipid-based nanocarriers for intranasal delivery in amyotrophic lateral...

Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder for which effective brain delivery of therapeutics remains challenging. Riluzole, a Biopharmaceutics Classification System class II drug used in the management of amyotrophic lateral sclerosis, exhibits low aqueous solubility and undergoes first-pass metabolism, which may limit its bioavailability. The present study aimed to develop and optimize riluzole-loaded nanostructured lipid carriers for intranasal delivery. Riluzole-loaded nanostructured lipid carriers were prepared by the melt-emulsification method and optimized using a four-factor, three-level Box-Behnken design. The effects of lipid composition ratio, surfactant concentration, sonication time, and stirring time on particle size, polydispersity index, and encapsulation efficiency were evaluated. The optimized formulation showed a particle size of 98.43 nm, a polydispersity index of 0.3, a zeta potential of -6.22 mV, an encapsulation efficiency of 89.4%, and a drug loading of 8.94%. Transmission electron microscopy demonstrated spherical nanoparticles, while differential scanning calorimetry and X-ray diffraction findings suggested reduced crystallinity and amorphization of riluzole within the lipid matrix. Fourier transform infrared spectroscopy indicated no significant drug-excipient incompatibility. The optimized formulation exhibited sustained drug release, with approximately 84% drug release over 24 h, and remained stable for 60 days at room temperature. These findings suggest that riluzole-loaded nanostructured lipid carriers are a promising lipid-based nanocarrier system for intranasal delivery and further biological evaluation for nose-to-brain drug delivery in amyotrophic lateral sclerosis.