Development of Engineered Micro-Particles via Spray Drying for Respiratory Drug Delivery

Abstract

In this study, respirable dry powders for the treatment of Pseudomonas aeruginosa and Burkholderia cepacia complex infections in cystic fibrosis patients were developed. The feasibility of spray drying aqueous solutions containing bacteriophages was investigated. Bacteriophages KS4-M, KS14 and ФKZ/D3 cocktail (active against P. aeruginosa or Burkholderia cepacia) were spray dried in solutions containing other excipients including trehalose and L-leucine. Acceptable process loss (0.4-0.8 log pfu), high delivery efficiency (69.7% of capsule load for the lead formulation), and desirable particle size (2.5-2.8 μm MMAD) were achieved. Then, L-leucine was substituted by and tested against D-leucine in the lead formulation to help eradicate bacteria biofilms. Similar morphologies and MMADs (3.25±0.03 μm and 3.82±0.04 μm for D- and L-leucine/trehalose) were achieved. Both formulations had acceptable total lung mass fractions (62.0±7.81% and 63.66±16.37% of emitted mass for D- and L-leucine/trehalose). Substitution L-leucine with D-leucine was found to be feasible.