Research Projects

Migraine is a neurological condition that causes severe, recurring headaches on one side of the head. It affects 18% of men and 43% of women, and is second among the world's disabling diseases and first among women. Although migraines are not life-threatening, they can lower the overall standard of living by having a negative impact on social and occupational functioning. Patients affected by frequent attacks may require preventive treatment. Zolmitriptan, a second-generation triptan, is recommended for people who suffer from migraine attacks, either with or without aura, and cluster headaches. It functions by targeting 5-HT (serotonin) 1B & 1D receptors and is particularly effective in reducing migraine symptoms such as pain, nausea, and sensitivity to light and sound. It is available in traditional tablet, orodispersible tablet, and nasal spray forms. However, administering medications orally when a migraine is present can be challenging due to acute nausea, poor GI absorption, or vomiting, and the bioavailability of nasal spray is very limited. Moreover, zolmitriptan has some side effects, such as nausea, dizziness, chest pain, and it is contraindicated for patients with certain medical conditions. Therefore, there is an urgent need for a new drug delivery method that reduces the current dose and dose-related peripheral side effects while delivering the drug to the brain within minutes. Zinc is an essential nutrient plays a critical role in the brain, influencing sensory perception and neurotransmission and activating networks for both pro-survival and pro-death neuronal signaling. It inhibits the N-methyl D-aspartate (NMDA) receptor, modulates postsynaptic activity and neural circuitry, enhancing migraine attack thresholds, and decreasing the frequency of migraine attacks. The co-administration of zinc with zolmitriptan may have a synergistic effect in acute migraine treatment. The direct nasal administration of zolmitriptan and zinc to deliver directly to the brain with a nanotechnological approach makes the transit easier for these agents and bypass the BBB, phagocytic, and efflux mechanisms hindering the possibility of reaching therapeutic concentrations in the brain. To achieve this, formulating a nanostructured lipid carriers (NLC) with low molecular weight, lipophilicity and smaller particle size to pass through the narrow gap of perineural pathway. The lipid-based NLCs can be coated with a surfactant that can enhance their adhesion to the nasal mucosa and facilitate their transport to the brain. This allows the substance to be discrete deposited and sustained on the olfactory epithelium. The aim is to improve the brain delivery of Zolmitriptan with Zinc sulfate for the treatment of acute migraine attacks through the olfactory epithelium, with a quick onset of action and less dose-related peripheral adverse effects.