Eletriptan HBr-loaded solid lipid nanoparticle-integrated microneedles: a targeted and minimally invasive approach...

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 conceptualised to encapsulate EHBr into solid lipid nanoparticles (SLNs) and deliver them via a transdermal microneedle (MN) 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 optimised 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 optimised 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.