CHARACTERIZATION OF AEROSOLS OF HUMAN RECOMBINANT DEOXYRIBONUCLEASE-I(RHDNASE) GENERATED BY JET NEBULIZERS

Recombinant human deoxyribonuclease I(rhDNase) is a new therapeutic ag ent developed to improve clearance of purulent sputum from the human a irways. It is delivered by inhalation. Four jet nebulizers, T Up-Draft II (Hudson), Customized Respirgard II (Marquest), Acorn II (Marquest) , and Airlife Misty (Baxter), were evaluated in vitro for their abilit y to deliver aerosols of rhDNase. The aerosols were generated from 2.5 -mL aqueous solutions of rhDNase, at concentrations of either 1 or 4 m g/mL. In all experiments, the Pulmo-Aide Compressor (De Vilbiss) was u sed to supply the air to the nebulizers. Between 20 and 28% of the rhD Nase dose initially placed in the nebulizers was delivered to the mout hpiece in the respirable range (1-6 mu m). Evaluation of the rhDNase f ollowing nebulization in all four devices indicated that there was no loss in enzymatic activity and no increase in aggregation. Circular di chroism spectrophotometry indicated there was no change in either the secondary or the tertiary structure in rhDNase following nebulization. These results show that all four nebulizers are essentially equivalen t in their ability to deliver respirable doses of rhDNase in an intact , fully active form. Changing the concentration of the solution in the nebulizer from 4 to 1 mg/mL rhDNase leads to a propertional reduction in the respirable dose delivered to the mouthpiece.