Pharmacodynamic and Physicochemical Evaluation of Intranasal Zolmitriptan-Loaded Nanostructured Lipid Carriers: for Enhanced Antimigraine Potential.

Migraine is a debilitating neuromuscular disorder marked by severe, one-sided headaches. Triptans, such as Zolmitriptan (ZMP), act as serotonin receptor agonists and are commonly used in migraine treatment. However, ZMP, classified under Bio-pharmaceutics Classification System Class III, suffers from low oral bioavailability (<4%), limiting its therapeutic efficacy. To address this, intranasal delivery using nanostructured lipid carriers (NLCs) has emerged as a promising strategy to enhance bioavailability and enable targeted brain delivery. The study aimed to improve the bioavailability of ZMP by developing intranasal NLCs and evaluating their potential for targeted brain delivery in migraine treatment. ZMP-loaded NLCs (ZMP-NLCs) were formulated using the hot melt emulsification method with high-speed stirring. The NLCs were optimized based on particle size, zeta potential, entrapment efficiency (EE), and drug release over 8 h. The optimized formulation consisted of 1% Glycerol Monostearate (solid lipid), 1% Capmul MCM (liquid lipid), and 1.5% Tween 80 (surfactant). The NLCs were characterized using Fourier transmission infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), and scanning electron microscopy (SEM) to confirm drug incorporation and particle morphology. Pharmacodynamic studies were conducted to assess brain delivery and antimigraine efficacy. The optimized NLC formulation exhibited a particle size of 233 ± 9.07 nm, a polydispersity index of 0.257 ± 0.03, a zeta potential of -42.8 ± 0.5 mV, an EE of 89.35 ± 0.9%, and a drug release of 87.1 ± 1.03% after 8 h. FTIR and XRD analyses confirmed the successful incorporation of ZMP into the NLCs without significant chemical interactions. SEM revealed uniform, spherical particles. Pharmacodynamic studies demonstrated effective brain delivery of ZMP, bypassing the blood-brain barrier, and significantly enhancing its antimigraine potential. This study highlights the potential of ZMP-NLCs for intranasal delivery. NLCs offer improved bioavailability and targeted brain therapy for effective migraine management. The findings suggest that NLCs are a promising approach for enhancing the therapeutic efficacy of ZMP.