Intranasal Application of Ubrogepant Nanoparticles Improve the Brain Penetration and Efficacy in Migraine
Abstract
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…
Read the paper
Related studies
- Calcium Ions in the Physiology and Pathology of the Central Nervous System
- AI-powered in silico twins: redefining precision medicine through simulation, personalization, and predictive healthcare
- In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene
- In Silico drug repurposing pipeline using deep learning and structure based approaches in epilepsy
- Targeting serotonin receptors with phytochemicals – an in-silico study
- In silico exploration of anti-prostate cancer compounds from differential expressed genes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.