Pulmonary targeting of nanoparticle drug matrices

Abstract

Background: Nanoparticle drug matrices using lipids or liposomes, with diameters of 40–300 nm, have recently been developed to encapsulate drugs like Insulin, Budesonide and Rifampicin for pulmonary delivery raising interest in their regional lung deposition. Methods: Lung deposition has so far been modeled using a one-dimensional transport equation, with or without moving airway boundaries and a lumped deposition term for particle diffusion, sedimentation and impaction. Here, a two-dimensional transport model has been developed with an explicit treatment of radial diffusion, the primary mechanism for nanoparticle deposition. Regional lung deposition was calculated using Weibel's whole lung model geometry during normal breathing and medical inhalation cycles. Conclusions: Model predictions agree well with measurements of total and pulmonary lung deposition for particles of 10 nm to 10 μm, with earlier models incorporating moving boundaries and aerosol dynamics and with the reported regional lung deposition of inhaled dry powder insulin. To simulate medical inhalation, the model was run with inhalation times from 2–6 sec and breath hold from 0–10 sec. A high and relatively invariant pulmonary deposition fraction between 70 and 95% was predicted for a broad nanoparticle size range (50–200 nm) for inhalation cycles with breathing rate between 500 and 2000 cm³ sec⁻¹ and breath hold of 5–10 sec. Thus, nanoparticles may be able to deliver consistent lung doses, over modest breath hold periods, even with intrapatient variability in breathing rate. A linearized nomogram was provided as a heuristic for design of nanoparticle drug matrices to target the pulmonary lung.