Propellant-Driven Aerosols of Proteins

ABSTRACT

The protein bovine gammaglobulin was combined with surfactants, suspended in dimethylether propellant, and delivered through metered-dose aerosol valves to produce small particle aerosols of protein. A fraction of the protein particles was of respirable size (≤ 4 μm aerodynamic diameter) as determined by cyclone or impactor aerosol sampling. Protein/surfactant molar rations of 1:1000 to 2000 produced the greatest percentage of respirable-sized protein particles. Excessive surfactant reduced the fraction of respirable-sized particles, whereas too little surfactant limited the suspension of protein in liquified propellant. Low protein/ surfactant densities in propellant increased the fraction of respirable-sized protein particles in aerosols, with 28%-36% of aerosolized protein of respirable size when protein concentrations were 0.2 mg/ml of propellant. Protein densities of up to 4 mg/ml in propellant could be delivered as aerosols, but with a reduced respirable fraction. Aqueous solutions of proteins at concentrations of 1 to 2 mg/ml combined with surfactants and then lyophilized to remove all water were aerosolized most effectively when suspended in propellant. Addition of glass beads to aerosol vials enhanced the dispersion of agitated protein/surfactant suspensions and improved protein aerosolization. Addition of 2%-4% ethanol in propellant increased the fraction of respirable-sized aerosol particles of protein. Mixtures of surfactants did not increase the total or respirable-sized protein particles in aerosols. The potential of propellant-driven aerosols for delivering therapeutic enzymes and antibodies, immunomodulating cytokines, and immunizing vaccines to the respiratory tract is discussed.