Characteristics of EPI-hNE4 Aerosol: A New Elastase Inhibitor for Treatment of Cystic Fibrosis

Abstract

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star^® and tested at three concentrations (2.5, 5, and 10 mg/mL). The inhaled mass was measured over 15 min. Particle size distribution was measured by cascade impaction. The effect was also tested of mixing EPI-hNE4 with a ^99mTc human serum albumin (HSA) tracer on the aerodynamic properties of the aerosol. The inhibitory activity of EPI-hNE4 after nebulization was assessed on purified HNE. The inhaled mass was 32.3 ± 3.5% (mean ± SD) after 10 min and 44.2 ± 3.8% (mean ± SD) after 15 min. Mass median aerodynamic diameter ranged between 1.2 and 1.8 μm. The ^99mTc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). ^99mTc activity was predictive of EPI-hNE4 mass distribution (y = 1.0278x - 1.6991, r = 0.89). The inhibitory capacity of aerosolized samples remained unchanged after up to 10 min of nebulization. EPI-hNE4 can be nebulized efficiently without decrease in its activity. Mixing this inhibitor with ^99mTc HSA should allow quantification of its deposition in CF patients.