An in vitro study on the deposition of micrometer-sized particles in the extrathoracic airways of adults during tidal oral breathing.

Deposition of particles in the aerodynamic diameter range of 0.5-6.7 µm was measured in nine replicas of the extrathoracic airways of adults with four sinusoidal patterns and oral breathing. The four chosen breathing patterns are typical of those occurring during natural resting breathing and during nebulization therapy. Additionally, deposition of micrometer-sized particles in the "Alberta Idealized Adult Throat," which was previously found useful in simulating the average deposition of particles during inhalation of constant flow rates, was measured during inhalation of the four sinusoidal patterns in this study. To reduce intersubject scatter in developing predictive correlations, the non-dimensional Reynolds (Re) and Stokes (Stk) numbers are used with the square root of the average cross sectional area of the oral airways as the characteristic diameter being found to reduce intersubject variability to the highest extent. Our best fit to the deposition data is given by η = [1 - 1/(1.51 x 10(5)(Stk(3.03)Re(0.25)) + 1)] x 100. Moreover, the "Alberta Idealized Adult Throat" is found to mimic average deposition, given in past in vivo studies, in the upper airways of adults during natural tidal breathing.

In vitro lung delivery of bacteriophages KS4-M and ΦKZ using dry powder inhalers for treatment of Burkholderia cepacia complex and Pseudomonas aeruginosa infections in cystic fibrosis.

AIMS: To determine the feasibility of formulating and aerosolizing powders containing bacteriophages KS4-M and ΦKZ for lung delivery and treatment of pulmonary Burkholderia cepacia complex and Pseudomonas aeruginosa infections. METHODS AND RESULTS: Endotoxin-removed bacteriophages KS4-M and ΦKZ were lyophilized in lactose/lactoferrin 60 : 40 w/w matrix and deagglomerated in a mixer mill (without beads) to formulate respirable powders. The powders were then aerosolized using an Aerolizer(®) capsule inhaler. Mass median aerodynamic diameter (MMAD) of this inhalable aerosol was determined using Andersen cascade impactor at 60 l min(-1). Measured MMAD for both types of powders was 3·4 µm, and geometric standard deviation was 1·9-2·0. Viability of bacteriophages delivered distal to an idealized mouth-throat replica was determined from bioassays of samples collected on filters placed after the idealized replica. As a percentage of inhaler load, amount of powder delivered distal to the mouth-throat replica, which is a measure of lung delivery, was 33·7 ± 0·3% for KS4-M and 32·7 ± 0·9% for ΦKZ. Titres collected downstream of the mouth throat were (3·4 ± 2·5) × 10(6) PFU for KS4-M with an Aerolizer capsule load of (9·8 ± 4·8) × 10(6) and (1·9 ± 0·6) × 10(7) for ΦKZ with an Aerolizer capsule load of (6·5 ± 1·9) × 10(7). CONCLUSIONS: Bacteriophages KS4-M and ΦKZ can be lyophilized without significant loss of viability in a lactose/lactoferrin 60 : 40 w/w matrix. The resulting powders can be aerosolized to deliver viable bacteriophages to the lungs. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of lactoferrin-based bacteriophage aerosol powders solidifies the ground for future research on developing novel formulations as an alternative to inhaled antibiotic therapy in patients with cystic fibrosis.