Dry powder nebulization of a recombinant surfactant protein C-based surfactant for treatment of acute respiratory distress syndrome

Introduction

Nebulization of pulmonary surfactant for treatment of ARDS represents a desirable therapeutic approach but was hitherto impossible under clinical conditions due to the technical limitations of currently available devices. In the present study we investigated a new dry powder nebulizer for administration of a recombinant surfactant protein C (rSP-C)-based surfactant.

Methods

The nebulizer device consists of a cylindrical glass housing that, at the bottom, ends up in a spherical lower housing part that serves as the dry powder reservoir. A gas inlet portion with a nozzle at its end is coaxially aligned with the housing, almost reaches the bottom of the dry powder reservoir, and induces aerosol generation when gas pressures between 1 and 2 bar are applied. The upper portion of the housing contains a cap with an aerosol exit port. Several nozzles ensure a discharge of unsuitably large aerosol particles. Aerosol characteristics were determined by laser diffractometry. The efficacy of an inhalative rSP-C surfactant application was assessed in three animal models of acute lung injury, including rabbits with acute lung injury due to either repetitive lavage with prolonged and injurious ventilation, or due to inhalative application of bleomycin at day 4, and bleomycin-challenged, spontaneously breathing mice.

Results

The generated aerosol had a mass median aerodynamic diameter of 1.6 μm, with 85% of all particles being smaller than 5 μm, and the average mass of surfactant being nebulized under these conditions was approximately 1 g/min. Biochemical and biophysical studies showed that the composition and surface tension reducing properties of the rSP-C surfactant remained unaltered after nebulization. In both rabbit models, administration of 130 mg/kg body weight rSP-C surfactant resulted in a far-reaching restoration of gas exchange and compliance. In bleomycin-challenged, spontaneously breathing mice, surfactant aerosolization resulted in a restoration of compliance.

Conclusion

Nebulizer characteristics and results from the in vivo studies suggest that the herein-described dry powder nebulizer might proffer for surfactant therapy of ARDS.