Mannitol delivery by vibrating mesh nebulisation for enhancing mucociliary clearance

Mucociliary clearance is compromised by airway surface liquid dehydration in respiratory disease states such as cystic fibrosis. Rehydration by hyperosmolar agents such as nebulised hypertonic saline and dry powder mannitol has demonstrated in vivo safety and efficacy for restoring mucociliary function. Mannitol, delivered as a nebulised formulation for this purpose, has not been investigated as yet. The current study examines the feasibility of delivering such a formulation using recent vibrating mesh technology. Nebulisation was conducted using an Aeroneb GoTM vibrating mesh nebuliser, and aerosol size was assessed by laser diffraction. Cascade impaction coupled with mass assay by high-performance liquid chromatography was used to confirm fluid uniformity and correlation with laser diffraction sizing. The following nebuliser formulations were prepared and aerosolised: deionised water, mannitol (150 mg/mL) aqueous solution, sodium chloride aqueous solution [0.2%, 1%, 3%, 5%, 7% (w/v)] and mannitol (150 mg/mL) in sodium chloride solution [0.2%, 1%, 3%, 7% (w/v)]. Mannitol aqueous solution was poorly nebulised, resulting in lengthy treatment times and large median droplet size. Addition of sodium chloride drastically improved nebuliser performance and aerosol characteristics. In vivo studies are necessary to confirm efficacy of nebulised mannitol. If substantiated, it could provide a pleasant-tasting alternative mucoactive agent with prolonged therapeutic action.