The Influence of Functional Carrier Particles (FCPs) on the Molecular Transport Rate Through the Reconstructed Bronchial Mucus: In Vitro Studies

Abstract

Mass transfer of deposited drug particles in the human lungs is an important factor in the effective drug delivery by inhalation. This study is focused on the basic research related to the possible acceleration of drug penetration toward the intended site of action through the barrier created by mucus layer. It is proposed that beneficial effect can be obtained by altering the mucus structure by inhaled functional carrier particles (FCPs) which are used to enhance pulmonary delivery of aerosolized powder drugs and simultaneously contain mucolytics (e.g., N-acetylcysteine: NAC). The FCPs were prepared by an optimized spray-drying technique and tested regarding their influence on the rheology of the reconstructed bronchial mucus and the transport rate of model drugs (Rhodamine B and Disodium Cromoglycate). The results indicate that the viscosity of mucus with high mucin concentration (i.e., reflecting a disease is reduced by up to 42 % depending on the concentration of added FCPs what is similar to the effect of pure NAC. Simultaneously, the effective diffusion coefficient Deff of the model drug through the mucus increased from 23 × 10-7 (pure mucus) to 42 × 10-7cm2/s (mucus modified by FCPs), and it was comparable to the effect obtained with pure NAC (51 × 10-7cm2/s). The results confirm that using mucolytics incorporated into powder particles (drug carriers) may be used to enhance mass transfer of inhaled aerosol drugs across the bronchial mucus layer.