Propellant-driven aerosols of functional proteins as potential therapeutic agents in the respiratory tract.
Aerosols of respirable-sized particles of functional proteins were delivered by volatile propellant from metered-dose aerosol canisters. The enzyme alkaline-phosphatase and a monoclonal antibody were lyophilized with surfactant and suspended in the aerosol propellant dimethylether. As much as 20 micrograms of functional protein, assessed by enzyme function or antibody binding activity, was delivered per 40 microliters of released propellant. Up to 25% of the protein was of respirable size (< or = 4 microns mass median aerodynamic diameter) when aerosolized proteins were sampled with a Casella cyclone. Respirable particles were derived from visible surfactant/protein complexes suspended in the liquified propellant and from propellant-soluble, nonsedimentable, surfactant/protein molecules that are probably reverse micelles. 10-14 days of propellant exposure in dimethylether increased protein solubility in the propellant, increased the total protein aerosolized and maintained or increased the quantity of respirable-sized protein molecules, as compared to the day aerosol vials were charged with propellant. Scanning electron microscopic studies of the respirable-sized protein/surfactant particles showed that they ranged in size from 0.07 to 3.25 microns in diameter, and they appeared to be chain aggregates of spherical subunits, 0.11 to 0.93 microns in diameter. This structural motif was common to both proteins. The possibility of delivering immunizing antigens, cytokines, passive antibodies and other therapeutic proteins to the respiratory tract using propellant-driven aerosols is discussed.
Department of Pathology and Microbiology, College of Veterinary Medicine, Kansas State University, Manhattan 66506.
A R
AR
Brown
J G
JG
Slusser
D000335:Aerosol Propellants; D000336:Aerosols; D000469:Alkaline Phosphatase / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D005612:Freeze Drying; D006801:Humans; D008738:Methyl Ethers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011506:Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D012140:Respiratory Tract Diseases / Q000188:drug therapy*; D013501:Surface-Active Agents / Q000008:administration & dosage
D000335:Aerosol Propellants; D000336:Aerosols; D000911:Antibodies, Monoclonal; D008738:Methyl Ethers; D011506:Proteins; D013501:Surface-Active Agents; C033413:dimethyl ether; D000469:Alkaline Phosphatase