Intranasal Application of Ubrogepant Nanoparticles Improve the Brain Penetration and Efficacy in Migraine

Background: Ubrogepant is a successful drug used for the therapy of migraine. Objectives: The objective of this work was to formulate a novel nanoparticle-based therapy using ubrogepant for optimum therapeutic efficacy by quick and sustained action. Materials and Methods: The ubrogepant nanoparticles were prepared using the emulsion solvent evaporation method using poly(lactic-co-glycolic) acid (PLGA) as the copolymer. These nanoparticles were tested by intranasal or intravenous route and in the in vitro assays for drug release and in vivo assays for exposure and activity in a migraine model. Results: The resulting nanoparticles had significant improvement in cellular uptake and reduced efflux in human colon adenocarcinoma cell line (Caco-2) cells when compared to the plain solution of ubrogepant. The in vivo studies indicated a higher concentration of ubrogepant in the brain, though the absorption is slightly delayed when the intranasal route administers the nanoparticles. The nitroglycerin (NTG)-induced migraine model in rats indicated that the nanoparticles by intranasal route showed significant improvement in locomotion, anxiety, pain behavior, and reduced pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 in trigeminal nuclei in the brain. A similar concentration of intravenous administration of ubrogepant was used as the comparator. Conclusion: Intranasal administration of ubrogepant nanoparticles shows potential as an effective drug delivery system for migraine.