An Electrospray Solution to the Pulmonary Delivery Problem

���This thesis addresses the critically poor efficacy of existing strategies to treat lung disease. A new device is developed using electrospray technology to deliver molecules into respiratory tissues via a bronchoscope. Novel diagnostic and therapeutic interventions are now possible by delivering appropriate molecules to target sites. The impact of this thesis is to facilitate earlier diagnosis of lung disease and enable local delivery of therapeutics to the lungs. Delivering molecules into the lung and airway tissues is challenging. The methodology is to design and implement an electrospray device for delivery of molecules to the respiratory tissues and to analyse its performance relative to existing delivery methodologies. A critical analysis of current electrospray methodologies of introducing molecules into tissues is presented. An electrospray device was fabricated for bronchoscopic clinical use based on a set of working parameters deduced from a rig and trailled in a large animal model. Molecules including DNA, siRNA, proteins, chemotherapeutics and marker dyes were delivered to tissues. The device's performance was analysed for consistency, targeted delivery, safety and efficacy. DNA and siRNA were delivered to human epithelial cell lines with up to 90% transfection. Proteins were delivered. Cisplatin, a chemotherapeutic, was delivered to cancer cells in a controllled experiment and killed >90% the cancer cells targeted. Methylene blue, the basis of an early stage cancer diagnostic test, was delivered to pigs, in vivo, using the device. It is concluded that an electrospray device will have a role in lung cancer diagnosis and therapy. The research outputs will ultimately be applicable to other disease types and to a wide range of therapeutic and diagnostic molecules. ���

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

National University of Ireland Maynooth

Year dc:date.issued

2010

Author dc:creator

• Maguire, Michael John

• Electronic Engineering

Language dc:language

en