Date of Award

1-1-2010

Document Type

Dissertation

Degree Name

Ph.D.

Organizational Unit

Daniel Felix Ritchie School of Engineering and Computer Science, Center for Orthopaedic Biomechanics

First Advisor

Corinne S. Lengsfeld, Ph.D.

Second Advisor

Thomas Anchordoquy

Third Advisor

James Wilson

Fourth Advisor

Andrei Kutateladze

Keywords

DNA, Electrohydrodynamic atomization, Liposome, Proteins, Structural stability

Abstract

With advances in drug research, the use of biological therapeutics is becoming a reality. Unfortunately, methods for processing and delivering these fragile macromolecules often limit their therapeutic potential. For this dissertation, we explore the aerosolization of macromolecules by way of electrohydrodynamic atomization (EHDA) and how this method can be used to process and deliver therapeutics. EHDA employs a high voltage to break a column of liquid into drops. It was unknown if or how the residual charge left of the resulting droplets would affect lung cells. An in vitro experiment was conducted to spray aerosolized DNA, by way of EHDA, onto human derived lungs cells to test for immunogenic and toxic effects. The lung cells displayed no immunogenic or toxic response to the DNA or high voltage. Previous researchers have used EHDA to aerosolize proteins with mixed results. This work sets forth a simplified thermodynamic theory and provides recommendations to pharmaceutical companies on how to design more stable protein formulations for aerosol processing or delivery. Finally, a new method of producing liposomes was created. It constructs the liposome one layer at a time. The inside of the liposome is sprayed by EHDA, with the lipid and drug in solution together. As the sprayed monolayer passes through a pool containing a solution of lipid in water, the second part of the bilayer attaches to the inner layer creating a complete bilayer liposome.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Michelle Zeles-Hahn

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

89 p.

Discipline

Biomedical Engineering

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