Nose-to-brain delivery of sumatriptan-loaded nanostructured lipid carriers: preparation, optimization, characterization and pharmacokinetic evaluation

Abstract

Objectives: Migraine is a neurological disorder with unilateral pulsatile headache which can affect the functions of sufferers. Migraineurs experience some undesirable symptoms such as pain, nausea, vomiting and in some cases auras which make the oral delivery non-selective. The lipid nanoparticles are considered as good carriers for nose-to-brain drug delivery. The present study aimed to formulate and evaluate a sumatriptan-loaded nanostructured lipid carrier (NLC). Methods: A drug-loaded NLC was optimized using D-optimal design of experiment and then the characterization of the formulated NLC including particle size, zeta potential, electron microscopy, thermal analysis, drug loading efficiency and release kinetics were carried out. Pharmacokinetic evaluations were also performed during an in-vivo study on Sprague–Dawley rats and neuropharmacokinetic parameters such as drug targeting efficiency (DTE) and direct transport percentage (DTP) were calculated. Key findings: The optimization of experiments led to nanoparticles with 101 nm mean diameter and polydispersity index (PDI) of 0.27. The drug entrapment efficiency (EE) for optimized nanoparticle was found to be 91.00%. DTE and DTP of intranasal-administered NLC were calculated 258.02% and 61.23%, respectively. Conclusions: Neuropharmacokinetic evaluation of intranasal NLC dispersion represents a suitable brain delivery system. The DTP of NLC formulation suggests the desirable entrance of sumatriptan into the brain.