Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemical and Biochemical Engineering

Supervisor

Dr. Sohrab Rohani

Abstract

Aerosols are an effective method to deliver therapeutic agents to the respiratory tract. Among aerosol generation systems, dry powder inhales have been attractive area of research for both local and systemic delivery of drugs. The challenge of any inhalation delivery system is to generate particles with an adequate range of particle sizes. In order to advance powder aerosol technologies, researchers have recognized the importance of investigating determinants affecting powder dispersion. The effect of particles’ surface characteristics, inhalation airflow rate, inhalation device, and development of an effective drug-carrier system are some of the fundamental areas that have been under investigation.

The aim of this thesis is to study parameters that govern the aerosolization characteristics of inhalation drug particles. In order to improve the therapeutic bioavailability of drugs, the current work demonstrates several techniques to manipulate the surface characteristics micro- and nanoparticles of two model drugs, namely; progesterone and 5-fluorouracil. With the recent interest in the development of targeted therapy, the present study introduces novel carriers for controlled delivery of magnetic nanoparticles to the respiratory tract. Management of nanoparticles physical characteristics as well as drug encapsulation efficiency was achieved via controlling variable formulation parameters.

The findings presented in this dissertation suggest a significant dependence of the aerosol characteristics on the characteristics of both drug and drug-carrier system. In this sense, with an increasing development of potent drug molecules for potential drug delivery via inhalation, it becomes quite pivotal to first accurately assess the determinant factors for lung deposition and dispersion behavior of dry powders. In this context, a novel setup for assessment of in-vitro aerosol deposition under the effect of an external magnetic field. The results suggest significant dependence of the particles dispersion behavior and deposition profile on their physical properties as well as the presence of magnetic field for their guidance to the required lung site. Encapsulating the drug in the proposed carrier system offered the advantage of controlled drug delivery; which is beneficial for therapeutic delivery of chemotherapeutic agents. Enhanced in-vitro cytotoxicity was achieved via controlling the formulation parameters in the engineered magnetic nanoparticles. Finally, this work presents alternative techniques of designing micro- and nano-vehicles for pulmonary drug delivery, with a localized deposition in the diseased area and the potential to reduce dose-related adverse effects.

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