화학공학소재연구정보센터
Journal of Applied Microbiology, Vol.110, No.1, 106-117, 2011
In vitro lung delivery of bacteriophages KS4-M and Theta KZ 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 Theta KZ for lung delivery and treatment of pulmonary Burkholderia cepacia complex and Pseudomonas aeruginosa infections. Methods and Results: Endotoxin-removed bacteriophages KS4-M and Theta KZ 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 (R) 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 center dot 4 mu m, and geometric standard deviation was 1 center dot 9-2 center dot 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 center dot 7 +/- 0 center dot 3% for KS4-M and 32 center dot 7 +/- 0 center dot 9% for Theta KZ. Titres collected downstream of the mouth throat were (3 center dot 4 +/- 2 center dot 5) x 106 PFU for KS4-M with an Aerolizer capsule load of (9 center dot 8 +/- 4 center dot 8) x 106 and (1 center dot 9 +/- 0 center dot 6) x 107 for Theta KZ with an Aerolizer capsule load of (6 center dot 5 +/- 1 center dot 9) x 107. Conclusions: Bacteriophages KS4-M and Theta KZ 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.