Author's School

School of Engineering & Applied Science

Author's Department/Program

Energy, Environmental and Chemical Engineering

Language

English (en)

Date of Award

January 2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Da-Ren Chen

Abstract

Chemoprevention is a promising approach to decrease the incidence of lung cancer in current and former smokers. Directly delivering drugs to the lung could lead to a high concentration in the target organ with a lower dose compared to other means of administration. The primary advantages of aerosol delivery in treating lung diseases include improving the bioavailability of the drug in the lung, decreasing the medicine dose, rapid action, and reducing the systemic toxicity as well as side effects. Spray techniques are widely used for aerosol delivery. Two spray techniques were evaluated in this study for their applications in lung cancer chemoprevention. One is the spray-drying process which was used to study the inhibitory effects of chemopreventive agents in lung tumorigenesis using the A/J mice model. The other is a twin-head electrospray: THES) to generate chemopreventive agent particles. Six single agents and three combinational agents, both natural and synthetic compounds, were investigated in the first part of this dissertation work. Polyphenon E and Polyphenon E without EGCG, which are mixtures of tea catechins, were studied to investigate the prevention mechanism of the mixture. Resveratrol was delivered in aerosol form to improve its efficacy, because it did not show any inhibitory effects in the dietary form due to its low bioavailability in the lung. Gefitinib and erlotinib were delivered via aerosols to decrease the dose to prevent severe skin toxicities associated with high dosages. The effect of aerosolized budesonide was studied. It was further combined with diet Polyphenon E, diet indole-3-carbinal, or oral pioglitazone in the animal study for the inhibitory effects over lung carcinogenesis. Aerosol characterization and drug concentration in different organs of mice, after exposure to the drug aerosols, were also carried out to facilitate the data interpretation. In the second part of this work, a twin-head electrospray system was developed to be used as an aerosol generator in animal studies of lung cancer chemoprevention. The system consists of two electrospray heads: one producing positively charged particles and the other for negatively charged ones. The coagulation between oppositely charged droplets generated by the THES was verified in three ways. The size evolution due to coagulation was studied for particles from 10 nm to 710 nm. The effect of the initial charge level on the coagulation process was investigated using dual-capillary ES. The residual charges on coagulated particles were measured. The particle transmission efficiency through the THES system was also characterized. The effect of particle mixing on the coagulation process was also investigated. The THES was then used to generate PLGA-based controlled release drug particles. Two drugs, budesonide and pioglitazone, were coated with PLGA using dual-capillary heads in the THES. Particles in various sizes and different drug-to-polymer ratios were prepared. The release profiles of prepared drug particles before and after coagulation were compared to investigate the release characteristics of THES-prepared drug particles. A promising application of the THES, as an electrospray inhaler, was also proposed.

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Permanent URL: http://dx.doi.org/10.7936/K7S180JX

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