Nanotechnology based approaches for the treatment of migraine using intranasal route

Abstract

Migraine is the 3rd most rated disease in world associated with socioeconomic load and as per gender statistics, women are affected more than men. Typical symptoms include nausea, vomiting, and increased sensitivity to strong light, loud noises, and odors. This acute headache if not treated may last for several hours to few days. Though the anti-migraine drug ergotamine was the first choice for many years its side-effects like habituation and its instability to heat, light, moisture led to decline of its use. Though the triptans proved to be a better choice than ergotamine, they exhibited low elimination half-life 2-4 h. ergotamine shows longer duration of action as compared to triptans and is equally potent and safe. Ergotamine acts on 5-HT receptors and serotonin receptors causing vasoconstriction. Drug exhibited short half-life (2h) and circulates in body for 24h whereas the low oral route bioavailability 12% and rectal bioavailability 27% rose the need for alternative non-invasive intranasal delivery route. Ergotamine combined with CNS stimulant caffeine as caffeine worked synergistically to relieve the migraine symptoms by forming soluble molecular complex that increase the ergotamine solubility with significant rate and extent of absorption. newlineThe use of nanotechnology coupled with intranasal delivery resulted in significant improvements in medication delivery with improved stability. The present study specifically aimed at development of polymer nanoparticles viz., nanosponges and microneedles, lipid nanoparticles (vesosomes) and lipid-polymer hybrid nanoparticles with permeation enhancers like caffeine. The optimized nanoparticulate formulations (nanosponges, microneedles, vesosomes and hybrid nanoparticles) were characterized using (Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM)), particle size, zeta potential,polydispersity index, solubility studies, % entrapment efficiency, in-vitro release studies, ex-vivo release studies, structural chemistry...