Current investigation aimed to develop a novel Amiloride loaded mucoadhesive nanoemulsion formulation for nose-to-brain delivery. Furthermore, nasal irritation study and histopathological examination of the nasal mucosa were also carried out to assess nonirritant nature of the nanoemulsion. The optimized formulation, surface epithelium lining and the granular cellular structure of the nasal mucosa were totally intact, whereas KCl caused major changes in the ultrastructure of mucosa. Amiloride loaded mucoadhesive nanoemulsion formulations are non toxic on nasal mucosa and can be administered by intranasal route for effective treatment of epilepsy.