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This digital document is a journal article from Journal of Aerosol Science, published by Elsevier in . The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: Jet nebulization is a common technique by which gene therapies can be delivered to the lungs, however current research has shown a reduction in activity and effectiveness of these treatments when not complexed with cationic agents. To date, a systematic investigation of chemical and mechanical degradation pathways has yet to be undertaken to identify the proximate cause of DNA instability. The purpose of this paper is to identify the dominant chemical and/or mechanical mechanism(s) by which DNA degrades when subjected to jet nebulization. Investigation of multiple degradation pathways revealed hydrodynamic shear to be primarily responsible for the observed loss in DNA integrity. Complexation of DNA with cationic agents polyethyleneimine or poly-L-lysine to DNA was sufficient to overcome these mechanical forces via a reduction in applied hydrodynamic forces.