GOALI: Modeling Electroporation-Mediated Drug Delivery

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9974185KrassowskaThis proposal seeks funding for an extended, six month visit by Dr. Wanda Krassowska, an Associate Professor of Biomedical Engineering at Duke University, to Genetronics, Inc. A drug delivery company, Genetronics specializes in developing technology and hardware that uses electroporation to deliver life-saving drugs or beneficial genes to patients. Electroporation is a broad-based technique in which strong electrical shocks are used to create pores in the cell membrane that enable biologically active molecules to enter the cell interior. Even though it is used quite extensively in biotechnology and medicine, electroporation is essentially empirical and its theoretical understanding lags behind practical applications. The PI has recently developed a model of electroporation that, in contrast to previous models, is very inexpensive to solve numerically. This feature makes it an ideal tool to study electroporation in systems that exhibit significant spatial variations, a feature occurring in nearly all experimental and clinical settings. Therefore, the objective of the PI's visit to Genetronics is to explore potential practical applications of this model in the area of electroporation-mediated drug delivery.The PI and the co-investigators from Genetronics have identified three possible areas in which the use of the model can impact the design of new devices and therapies: (1) the role of pulse shape, strength, duration, and frequency on pore creation and uptake of active molecules; (2) cell survival during electroporation with very long, low intensity pulses; and (3) multi-pulse protocols for delivery of DNA and drugs into cells.The PI will be responsible for implementing the model on the company computer and customizing it for a particular application. The industrial collaborators will contribute to the model development by supplying information on the objectives of the electroporation treatment, the geometry of the preparation, shock protocols, and drug characteristicsThe Genetronics scientists will also evaluate how well the model reproduces, explains, and predicts experimental results and will provide the PI with the feedback for the next stage of model development. If, as a result of the collaboration proposed in this application, the model will be able to predict the transfer of drugs and genetic material to cells, it will substantially advance the scientific foundations of the electroporation-mediated drug delivery.