Magnetically targeted deposition and retention of particles in the airways for drug delivery.

摘要

This thesis examines the mechanisms of magnetic particle deposition and retention in human airways for magnetically targeted drug delivery. As this is a novel application, fundamental studies were performed to establish the necessary background knowledge for further development.;For retention, clearance of particles due to motion of the mucus lining of the airways must be overcome. Particle retention was studied in vitro using various liquids to simulate mucus and identify relevant parameters. An ex vivo animal tissue model was used to demonstrate feasibility. Retention of 3-5 mum diameter iron particles was achieved at reduced liquid/mucus viscosities. Larger (∼100 mum) particles were retained at normal mucus viscosities. The size dependence shows that particle aggregation after deposition is crucial for effective retention.;In vitro retention experiments showed aggregate size is correlated with liquid viscosity, i.e. formation of aggregates is limited by forces opposing particle motion along the mucus layer interface. To determine these forces, particle motion on various air-liquid interfaces, chosen to simulate different mucus properties in isolation, was studied. When surfactants are present, as in the mucus layer, particle motion is limited by a velocity-dependent surface tension gradient as well as viscous drag.;Pulling particles through the mucus layer into the tissue beneath was also considered as a potential retention strategy. The force required to pull particles through the mucus layer was also studied using various liquids to simulate mucus properties. In addition to the surface tension force holding the particles at the interface, hydrodynamic forces must be overcome to pull particles into or out of a liquid film such as the mucus layer.;Magnetic particle deposition from an aerosol in simulated airway conditions was studied using numerical and experimental models. The model results showed qualitative agreement; discrepancies were due to particle aggregation, which enhances deposition. Aerosol flow rate had a limited effect; the main factor in effective deposition was the proximity of the particle trajectories to the magnets. This spatial bias shows the importance of particle distribution in the flow as well as magnetic field geometry. These studies demonstrated the feasibility of capturing magnet particles from aerosol in airway conditions.