Dry Powder Inhaler Formulation of Lactobacillus rhamnosus GG Targeting Pseudomonas aeruginosa Infection in Bronchiectasis Maintenance Therapy

Abstract

The inhaled delivery of lactic acid bacteria (LAB) probiotics has been demonstrated to exert therapeutic benefits to the lungs due to LAB’s immunomodulatory activities. The development of inhaled probiotics formulation, however, is in its nascent stage limited to nebulized LAB. We developed a dry powder inhaler (DPI) formulation of lactobacillus rhamnosus GG (LGG) intended for bronchiectasis maintenance therapy by spray freeze drying (SFD). The optimal DPI formulation (i.e., LGG: mannitol: lactose: leucine = 35: 45: 15: 5 wt.%) was determined based on the aerosolization efficiency (86% emitted dose and 26% respirable fraction) and LGG cell viability post-SFD (7 log CFU/mL per mg powder). The optimal DPI formulation was evaluated and compared to lyophilized naked LGG by its (1) adhesion capacity and cytotoxicity to human lung epithelium cells (i.e., A549 and 16HBE14o- cells) as well as its (2) effectiveness in inhibiting the growth and adhesion of Pseudomonas aeruginosa to lung cells. The optimal DPI of LGG exhibited similar non-cytotoxicity and adhesion capacity to lung cells to naked LGG. The DPI of LGG also inhibited the growth and adhesion of P. aeruginosa to the lung cells as effectively as the naked LGG. The present work established the feasibility of delivering the LAB probiotic by the DPI platform without adversely affecting LGG’s anti-pseudomonal activities.