Evaluation of Brain Targeting Potential of Zolmitriptan Mucoadhesive Nanoparticles for Intranasal Drug Delivery

Abstract

Background: Hydrophilic drugs are poor applicants for brain targeting via oral route due to the presence of a blood-brain barrier that allows only small lipophilic molecules to freely access the brain. Due to unique anatomical connections between the nasal cavity and the brain, intranasal administration can be explored for drug delivery to the brain directly that circumvents the blood-brain barrier too. Objectives: Zolmitriptan is a widely used antimigraine drug, and its brain targeting by nasal route in the form of mucoadhesive nanoparticles is more effective in migraine treatment as it provides fast relief and good bioavailability as compared to its oral drug delivery. In the present study, zolmitriptan mucoadhesive nanoparticles were prepared to improve the bioavailability and brain targeting for the better management of Migraine attacks. Methods: The mucoadhesive polymeric nanoparticles of zolmitriptan were formulated by a modified ionic gelation method using thiolated chitosan. The pharmacokinetic parameters were counted in male Wistar rats by intranasal and oral delivery of the anti-migraine drug zolmitriptan and compared statistically. The concentration of zolmitriptan in the blood plasma and brain samples was determined by using the liquid-liquid extraction method followed by a reversed-phase highperformance liquid chromatography (RP-HPLC) analysis. The pharmacodynamic analysis was conducted in adult male Swiss albino mice by behavioral models, a light/dark box model, and acetic acid-induced writhing (abdominal stretching or constriction). These tests were used to reproduce the important associated symptoms of migraine viz. hyperalgesia (nociceptive sensitization) and photophobia to assess the therapeutic potential of intranasal delivery of nanoparticles antimigraine activity. Results: The absolute bioavailability accessed for Zolmitriptan nanoparticles by IN route was found to be very high (193%), suggesting that the sufficient amount of drug transported by nanoparticles and DTE ratio was calculated as 2.8. Moreover, it revealed better nose-to-brain transport by zolmitriptan nanoparticles as compared to oral delivery in male Wistar rats. A significant increase in the tolerance capacity of animals to bright light and a fall in the number of stretching in mice suggested the better management of migraine-associated symptoms by the zolmitriptan nanoparticles. Conclusion: Thus, the present study confers the significance of nasal drug delivery for brain targeting of zolmitriptan nanoparticles for the treatment of migraine.