Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.
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 (99m)Tc 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 microm. The (99m)Tc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). (99m)Tc 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 (99m)Tc HSA should allow quantification of its deposition in CF patients.
Grimbert
D
D
INSERM EMI-U 00-10, IFR 120, Groupes de Pneumologie et Enzymologie, Tours, France.
Vecellio
L
L
Delépine
P
P
Attucci
S
S
Boissinot
E
E
Poncin
A
A
Gauthier
F
F
Valat
C
C
Saudubray
F
F
Antonioz
P
P
Diot
P
P
D000280:Administration, Inhalation; D000336:Aerosols; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004867:Equipment Design; D006801:Humans; D016014:Linear Models; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011506:Proteins / Q000008:administration & dosage*; D015843:Serpins
D000336:Aerosols; D011506:Proteins; D015843:Serpins; C075177:SERPINB1 protein, human