Electrohydrodynamic Atomization for Improved Macromolecular Drug Delivery

<p>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 <em>in vitro</em> 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.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Year dc:date.available

2010

Author dc:creator

• Zeles-Hahn, Michelle

Contributors dc:contributor

• Corinne S. Lengsfeld, Ph.D.
• Thomas Anchordoquy
• James Wilson
• Andrei Kutateladze

• DNA
• Electrohydrodynamic atomization
• Liposome
• Proteins
• Structural stability
• Biomedical Engineering and Bioengineering

Statement dc:rights

• <p>Copyright is held by the author. User is responsible for all copyright compliance.</p>

Language dc:language

en

Repository record dc:identifier

https://digitalcommons.du.edu/etd/959

OAI identifier oai:identifier

oai:digitalcommons.du.edu:etd-1958