Eletriptan HBr Loaded Solid Lipid Nanoparticle Integrated Microneedles: A Targeted and Minimally Invasive Approach for Migraine Management

Eletriptan hydrobromide (EHBr) exhibits poor oral bioavailability due to extensive first-pass metabolism by CYP3A4 and P-glycoprotein mediated efflux at the blood brain barrier. Therefore, this study was conceptualized to encapsulate EHBr into solid lipid nanoparticles (SLNs) and deliver them via a transdermal microneedle array (MNs) array for targeted brain delivery. SLNs were formulated using a lipid matrix comprising glyceryl monostearate, stearic acid, and hydrogenated soy phosphatidylcholine, with Poloxamer-188 as the emulsifier. The optimized SLNs showed a particle size of 165.5 ± 71.75 nm, zeta potential of -27.1 ± 4.48 mV, and entrapment efficiency of 63.25 ± 1.44%, and were incorporated into polymer-based MNs. The optimized MNs exhibited high drug content (93.65 ± 1.39%), good mechanical strength (P < 0.05), excellent insertion efficiency (F = 17.83, P = 3.03 × 10−8), and rapid in situ dissolution. Ex vivo studies demonstrated sustained EHBr release (89.67 ± 1.03% over 24 h), following first-order kinetics (R2 = 0.998) with non-Fickian diffusion (n = 0.79). FTIR and XRD analyses confirmed drug excipient compatibility and formulation stability. In vivo evaluation in Wistar rats revealed significant antinociceptive, anxiolytic, and anti-photophobic effects (p ≤ 0.027), and reduced neurogenic inflammation confirming the enhanced brain delivery and bioavailability of EHBr.