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Modeling of In Vivo Tissue Electroporation and Cellular Uptake Enhancement

Bradley Boyd, Sid Becker

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Abstract

Electroporation of biological tissue is a phenomenon where an electric field above a certain threshold introduces hydrophilic pores into the cell membrane that the drug is able to diffuse through - referred to as cellular drug uptake. The primary motivation of this study is to develop a macroscopic model of drug transport in electroporated tissue to determine the cellular drug uptake, achieved by relating the cell permeability to the extent of electroporation. Many aspects require consideration when developing a model that couples electroporation to drug transport. The diffusive drug transport in tissue consists of two main aspects: drug diffusion and cellular drug uptake. Additional aspects of electroporation are pore resealing and irreversible electroporation, which influence the cellular drug uptake. Pore resealing results in transient relaxation of the cell membrane permeability after reversible electroporation. Whereas irreversible electroporation, which introduces irreversible pores causes cell death. The model enables optimization of the desired effects of electroporation. It allows the electrode positions and pulse voltage to be determined to minimize cell death and maximize reversible electroporation for increased drug uptake to living cells. Modeling of an electroporation case is now possible given the appropriate parameters and property values of the system of interest providing valuable insight and predictions.

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Electroporation of biological tissue is a phenomenon where an electric field above a certain threshold introduces hydrophilic pores into the cell membrane that the drug is able to diffuse through - referred to as cellular drug uptake. The primary motivation of this study is to develop a macroscopic model of drug transport in electroporated tissue to determine the cellular drug uptake, achieved by relating the cell permeability to the extent of electroporation. Many aspects require consideration when developing a model that couples electroporation to drug transport. The diffusive drug transport in tissue consists of two main aspects: drug diffusion and cellular drug uptake. Additional aspects of electroporation are pore resealing and irreversible electroporation, which influence the cellular drug uptake. Pore resealing results in transient relaxation of the cell membrane permeability after reversible electroporation. Whereas irreversible electroporation, which introduces irreversible pores causes cell death. The model enables optimization of the desired effects of electroporation. It allows the electrode positions and pulse voltage to be determined to minimize cell death and maximize reversible electroporation for increased drug uptake to living cells. Modeling of an electroporation case is now possible given the appropriate parameters and property values of the system of interest providing valuable insight and predictions.

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Available abstract

Electroporation of biological tissue is a phenomenon where an electric field above a certain threshold introduces hydrophilic pores into the cell membrane that the drug is able to diffuse through - referred to as cellular drug uptake. The primary motivation of this study is to develop a macroscopic model of drug transport in electroporated tissue to determine the cellular drug uptake, achieved by relating the cell permeability to the extent of electroporation. Many aspects require consideration when developing a model that couples electroporation to drug transport. The diffusive drug transport in tissue consists of two main aspects: drug diffusion and cellular drug uptake. Additional aspects of electroporation are pore resealing and irreversible electroporation, which influence the cellular drug uptake. Pore resealing results in transient relaxation of the cell membrane permeability after reversible electroporation. Whereas irreversible electroporation, which introduces irreversible pores causes cell death. The model enables optimization of the desired effects of electroporation. It allows the electrode positions and pulse voltage to be determined to minimize cell death and maximize reversible electroporation for increased drug uptake to living cells. Modeling of an electroporation case is now possible given the appropriate parameters and property values of the system of interest providing valuable insight and predictions.

Key concepts: Electroporation, Membrane permeability, Biophysics, Irreversible electroporation, In vivo, Drug delivery, Permeability (electromagnetism), Membrane

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