Journal of Aerosol Medicine and Pulmonary Drug Delivery 2011-04-01

Surfactant and perfluorocarbon aerosolization by means of inhalation catheters for the treatment of respiratory distress syndrome: an in vitro study.

Xabier Murgia, Elena Gastiasoro, Victoria Mielgo, Francisco Alvarez-Diaz, Hector Lafuente, Adolf Valls-i-Soler, Miguel Angel Gomez-Solaetxe, Juan Luis Larrabe, Carmen Rey-Santano

Index: J. Aerosol Med. Pulm. Drug Deliv. 24(2) , 81-7, (2011)

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Abstract

The aerosolization of perfluorocarbons or surfactant has emerged as a feasible alternative to instillation, for the treatment of experimental respiratory distress syndrome. However, the biophysical properties that make these compounds useful in such therapies, significantly affect the performance of nebulizers. Therefore, in vitro studies are required to assess the suitability of new aerosolization technologies for use with these compounds.The aim of the present in vitro study was to investigate the influence of the biophysical properties of perfluorocarbons (PFD, FC75, and PFOB) and a natural porcine surfactant, Curosurf®; on aerosolization and to assess the suitability of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, IC-1.4) coupled to a jet nebulizer, for aerosol delivery of these compounds.With IC-1.23 significantly higher aerosol production rates were achieved (p < 0.0001), ranging between 6.05 ± 0.17 mL/min (FC75) and 1.94 ± 0.09 mL/min (Curosurf®), and lower percentage losses of the compound (5-21%), compared to IC-1.1 and IC-1.4 catheters. The lowest aerosolization rates were produced with IC-1.4 ranging from 0.58 ± 0.02 mL/min (FC75) to 0.14 ± 0.01 mL/min (Curosurf®), and this catheter also resulted in the highest percentage losses (25-60%). The mass median aerodynamic diameter (MMAD) ranged between 0.77 μm (PFD) and 8.29 μm (Curosurf®) with IC-1.1, whereas higher MMAD values, of between 4.84 μm (FC75) and 13.42 μm (PFOB), were observed with IC-1.23. Regardless of the catheter used during aerosolization, the perfluorocarbon with the highest kinematic viscosity showed the lowest aerosolization and emission rates and vice versa, which reveals the substantial contribution of this parameter that should accordingly be considered in the design of perfluorocarbon aerosol drug delivery systems.Jet aerosolization of perfluorocarbons or surfactant with the intratracheal inhalation catheters seems to be a suitable method for treating experimental respiratory distress syndrome, because it delivers relatively high doses of perfluorocarbons and surfactant to the lungs in a respirable size droplets.