Application of corona ions produced in air to B16F10 murine melanoma cells in vitro and in animal models resulted in the transport of molecular therapeutics across the cell membrane. This work presents the development of new methods for drug and gene delivery based upon similar principles as the traditional electrode driven membrane destabilization processes known as electroporation. This was achieved with non-contact corona ion deposition that temporarily increased the permeability of cell membranes. Interaction of corona charge with biological cells was studied and their potential for molecular delivery was established. Molecular delivery was first demonstrated in vitro using tracer molecules followed by in vitro delivery of the cytotoxic drug bleomycin. Building upon these results, the delivery of bleomycin coincident with ion deposition was xxi shown to significantly slow the growth of very aggressive solid tumors in animal models, compared to drug alone or no treatment. Delivery of plasmid DNA to cells in the skin of animal models indicated that application of corona ions (both positive and negative) to live tissue produced a four to six fold increase in gene expression. As this is the first significant study of the interaction and impact of corona ions on the delivery of drug and plasmid DNA to biological cells, numerous fundamental investigations were performed and discussed. A charge dose dependence was observed and physical mechanistic models were proposed. A model of cell resealing time constant following corona ion exposure was developed and demonstrated a reasonable prediction of experimental findings. The foundation laid by this work may enable continued exploration and use of corona ion deposition in the future as a new and promising physical method for drug and gene delivery.

Electroporation is a methodology for the introduction of drugs and genes into cells. This technique works by reducing the exclusionary nature of the cell membrane [125, 129, 186, 189]. Electroporation has successfully been used in electrochemotherapy and electrogenetherapy [57, 68, 86, 87, 110, 112, 131]. The two major components of electroporation are an induced transmembrane potential and the motion of the deliverable through a compromised cell membrane into the target cell [38, 55, 62, 114, 131]. These two components are both dependent on the electrophoretic motion of charged species in an applied electric field [45, 64, 75, 77, 177]. Currently, the methods outlined for understanding electroporation have been focused on either a phenomenological perspective, e.g. what works, or modeling the electric fieldstrength in certain regions [12, 56, 87, 129, 146, 204, 205]. While this information is necessary for the clinician and the laboratory scientist, it doesn't expand the understanding of how electric field mediated drug and gene delivery works or EFMDGD. To increase the understanding of EFMDGD, new models are required that predict the motion of ions and deliverables through tissues to target areas [75, 77]. This document examines the design and creation of an electric field mediated drug and gene delivery model, EFMDGDM. Two example scenarios, ionic motion in tissues and gel electrophoresis, are examined in depth using the EFMDGDM. The model requires tuning for each scenario but only utilizes experimental parameters and one tunable parameter that is computed from regressed experimental data. The EFMDGDM successfully describes the two examples. Future work will incorporate the EFMDGDM as the backbone of an electric field mediated drug and gene delivery modeling package, EFMDGDMP.