Magnetically targeted deposition and retention of particles in the airways for drug deliveryReport as inadecuate

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magnetic targeting, magnetic aerosol, mucus clearance, tensiometry, magnetic particles, Marangoni effect, air-liquid interfaces

Ally, Javed Maqsud

Supervisor and department: Amirfazli, Alidad Mechanical Engineering

Examining committee member and department: Lange, Carlos Mechanical Engineering Bhattacharjee, Subir Mechanical Engineering Yeung, Anthony Chemical Engineering Acosta, Edgar Chemical Engineering and Applied Chemistry, University of Toronto Mitra, Sushanta Mechanical Engineering

Department: Department of Mechanical Engineering


Date accepted: 2010-04-13T20:56:53Z

Graduation date: 2010-06

Degree: Doctor of Philosophy

Degree level: Doctoral

Abstract: 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.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.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 μm diameter iron particles was achieved at reduced liquid-mucus viscosities. Larger ~100 μm 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.

Language: English

DOI: doi:10.7939-R3HG8C

Rights: Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.

Author: Ally, Javed Maqsud



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