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Abstract
The work described in this thesis investigated the possibility that respiratory tract deposition of inhaled, high aspect ratio aerosol particles could be influenced through control of particle orientations, for the purpose of targeting aerosol drug delivery to specific locations within the lung. Initial experiments were conducted to demonstrate that high aspect ratio cromoglycic acid particles loaded with iron oxide nanoparticles would align with magnetic field lines. Collection of the iron oxide loaded particles on polycarbonate membrane filters increased with a low gradient magnetic field applied parallel to the face of the filters, and alignment of the particles in the direction of field lines was clearly visible in scanning electron micrographs of the filters. Further, more demanding, experiments were then conducted in a physical model of the small, bifurcating airways found in the lung. These experiments provided proof that magnetic alignment of high aspect ratio particles can be used to increase their deposition in small airway bifurcations.
Supplementary bench experiments were conducted to examine the delivery of high aspect ratio powders of ciprofloxacin, a broad-spectrum antibiotic, and paclitaxel, a chemotherapeutic agent, from a commercial dry powder inhaler. Powders were studied with and without the addition of iron oxide nanoparticles. The results of the experiments were mixed; while the measured lung doses penetrating a model mouth-throat geometry were reasonably high, these doses included significant fractions of agglomerates, which no longer exhibited the elongated nature of the individual particles.
Finally, experiments were performed to investigate the feasibility of measuring regional lung deposition of inhaled iron oxide nanoparticles using MRI. Mice were exposed nose-only to nebulized superparamagnetic iron oxide nanoparticles, and regional concentrations of iron in the left and right lung were quantified by measuring the longitudinal relaxation times (T1 ) of the lung tissue in exposed mice, compared to a baseline group. In addition, a very small pilot study was conducted in mechanically ventilated rabbits exposed intratracheally to iron oxide loaded cromoglycic acid particles, demonstrating combined targeting by magnetic alignment and subsequent assessment using MRI. Such an approach shows considerably promise for future treatment of localized lung disease.
