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Intracellular Protein Delivery and Gene Transfection by Electroporation Using a Microneedle Electrode Array

Authors

  • Seong-O Choi,

    1. School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
    2. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
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  • Yeu-Chun Kim,

    1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
    2. Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea
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  • Jeong Woo Lee,

    1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
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  • Jung-Hwan Park,

    1. Department of BioNano Technology and Gachon, BioNano Research Institute, Gachon University, Sungnam, 461-701, Republic of Korea
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  • Mark R. Prausnitz,

    Corresponding author
    1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
    • School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
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  • Mark G. Allen

    Corresponding author
    1. School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
    2. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
    • School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Abstract

The impact of many biopharmaceuticals, including protein- and gene-based therapies, has been limited by the need for better methods of delivery into cells within tissues. Here, intracellular delivery of molecules and transfection with plasmid DNA by electroporation is presented using a novel microneedle electrode array designed for the targeted treatment of skin and other tissue surfaces. The microneedle array is molded out of polylactic acid. Electrodes and circuitry required for electroporation are applied to the microneedle array surface by a new metal-transfer micromolding method. The microneedle array maintains mechanical integrity after insertion into pig cadaver skin and is able to electroporate human prostate cancer cells in vitro. Quantitative measurements show that increasing electroporation pulse voltage increases uptake efficiency of calcein and bovine serum albumin, whereas increasing pulse length has lesser effects over the range studied. Uptake of molecules by up to 50% of cells and transfection of 12% of cells with a gene for green fluorescent protein is demonstrated at high cell viability. It is concluded that the microneedle electrode array is able to electroporate cells, resulting in intracellular uptake of molecules, and has potential applications to improve intracellular delivery of proteins, DNA, and other biopharmaceuticals.

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