Rational design and characterisation of intranasal gel incorporating eletriptan HBr-loaded solid lipid nanoparticles for enhanced brain delivery in migraine

Eletriptan HBr-loaded solid lipid nanoparticles (ESLN) were designed for brain delivery by circumventing first-pass metabolism and the blood-brain barrier. The formulation combines biocompatible polymers with the permeability-enhancing properties of lipids. A central composite design was employed to optimize formulation variables to achieve ESLN with optimal physicochemical characteristics. The optimized ESLN showed a mean particle size of 257.4 ± 106.3 nm, zeta potential of −23.3 ± 4.25 mV, and entrapment efficiency of 71.77 ± 0.58%. SEM reveals smooth-surfaced, spherical nanoparticles. In situ nasal gel of ESLN was optimized using a 32 full factorial design. The gel exhibited a gelation temperature of 34.7 ± 0.6 °C and a gelation time of 68 ± 4.58 s, with a viscosity ranging from 120 ± 8.6 cPs at 25 °C to 11,230 ± 255 cPs at 35 °C. Ex vivo studies demonstrated 65.29 ± 3.12% cumulative Eletriptan HBr (EBr) permeation from the ESLN gel, compared to 51.69 ± 3.30% from the plain gel over 24 h. Brain biodistribution studies in Wistar rats demonstrated enhanced brain exposure of EBr following administration of the ESLN gel, with a Cmax of 1542.284 ng/g and an AUC0-∞ of 22,910.8 ng·h/g, compared with the plain EBr-loaded gel. Histology of the brain and nasal mucosa confirmed the formulation’s safety.