Non invasive contact electrodes for in vivo localized cutaneous electropulsation and associated drug and nucleic acid delivery.

For an effective tissue controlled electropermeabilization as requested for electrochemotherapy and electrogenotherapy, it is very important to have informations about the electric field distribution provided by a defined set of electrodes. Computer simulations using the finite element models approach predicted the associated field distributions and currents. Phantoms made of gels with well-defined electrical conductance were used to measure the current responses of a new electrode geometry (wires), A good agreement between the measured and predicted currents was observed supporting the validity of the prediction for the field distribution. Field distribution was observed to be very localized and highly homogeneous with the new concept of contact wire electrodes. They allowed to focus the field effect along the surface of the tissue to induce a controlled release of drugs or plasmids. Non invasive (contact) electrodes can be moved rapidly on the body and avoid puncturing the skin and the tissue. They can be used for large surface effects, to treat the skin and subcutaneous tumors. The use of contact electrodes after drug or DNA intradermal injection were validated by clinical treatment of large surface skin tumors and by in vivo imaging of permeabilization or of gene expression.

[1]  D. Wells,et al.  Electroporation for gene transfer to skeletal muscles: current status. , 2004, BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy.

[2]  J Teissié,et al.  Electropermeabilization of mammalian cells. Quantitative analysis of the phenomenon. , 1990, Biophysical journal.

[3]  G. A. Hofmann,et al.  Instrumentation and electrodes for in vivo electroporation. , 2000, Methods in molecular medicine.

[4]  H. Aihara,et al.  Gene transfer into muscle by electroporation in vivo. , 1998, Nature biotechnology.

[5]  M. Rols,et al.  In vivo electrically mediated protein and gene transfer in murine melanoma , 1998, Nature Biotechnology.

[6]  R. Malone,et al.  Cutaneous transfection and immune responses to intradermal nucleic acid vaccination are significantly enhanced by in vivo electropermeabilization. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[7]  Muriel Golzio,et al.  Effect of electric field vectoriality on electrically mediated gene delivery in mammalian cells. , 2004, Biochimica et biophysica acta.

[8]  F Andreand DNA electrotransfer: its principles and an updated review of its therapeutic applications , 2004 .

[9]  M. Rols,et al.  Direct visualization at the single-cell level of electrically mediated gene delivery , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Hui,et al.  Using surface electrodes to monitor the electric-pulse-induced permeabilization of porcine skin. , 2000, Methods in molecular medicine.

[11]  Mojca Pavlin,et al.  Effect of electric field induced transmembrane potential on spheroidal cells: theory and experiment , 2003, European Biophysics Journal.

[12]  Damijan Miklavčič,et al.  Changing electrode orientation improves the efficacy of electrochemotherapy of solid tumors in mice , 1996 .

[13]  D Miklavcic,et al.  The importance of electric field distribution for effective in vivo electroporation of tissues. , 1998, Biophysical journal.

[14]  J Teissié,et al.  Electrochemotherapy of horses. A preliminary clinical report. , 2002, Bioelectrochemistry.

[15]  J Teissié,et al.  Time courses of mammalian cell electropermeabilization observed by millisecond imaging of membrane property changes during the pulse. , 1999, Biophysical journal.

[16]  Darius Moradpour,et al.  In vivo gene electroinjection and expression in rat liver , 1996, FEBS letters.

[17]  M. Jaroszeski,et al.  Intradermal delivery of interleukin-12 plasmid DNA by in vivo electroporation. , 2001, DNA and cell biology.

[18]  Shulin Li,et al.  Regression of High-Grade Malignancy in Mice by Bleomycin and Interleukin-12 Electrochemogenetherapy , 2006, Clinical Cancer Research.

[19]  Muriel Golzio,et al.  Cell and animal imaging of electrically mediated gene transfer. , 2003, DNA and cell biology.

[20]  Muriel Golzio,et al.  New anti angiogenesis developments through electro-immunization: optimization by in vivo optical imaging of intradermal electro gene transfer. , 2007, Biochimica et biophysica acta.

[21]  R. Hoffman,et al.  Visualizing gene expression by whole-body fluorescence imaging. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M J Jaroszeski,et al.  Novel electrode designs for electrochemotherapy. , 1997, Biochimica et biophysica acta.

[23]  D Miklavcic,et al.  A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. , 2000, Biochimica et biophysica acta.

[24]  Damijan Miklavcic,et al.  Techniques of signal generation required for electropermeabilization. Survey of electropermeabilization devices. , 2004, Bioelectrochemistry.

[25]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[26]  H. Yamagishi,et al.  Electrochemo-gene therapy of cancer: intratumoral delivery of interleukin-12 gene and bleomycin synergistically induced therapeutic immunity and suppressed subcutaneous and metastatic melanomas in mice. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[27]  D. Miklavčič,et al.  Calculation of the electrical parameters in electrochemotherapy of solid tumours in mice , 1998, Comput. Biol. Medicine.

[28]  J. Gehl,et al.  Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research. , 2003, Acta physiologica Scandinavica.

[29]  Damijan Miklavčič,et al.  Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy , 2006 .

[30]  I. G. Abidor,et al.  Studies of cell pellets: II. Osmotic properties, electroporation, and related phenomena: membrane interactions. , 1994, Biophysical journal.

[31]  P Raskmark,et al.  In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. , 1999, Biochimica et biophysica acta.

[32]  S. Sukharev,et al.  In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. , 1991, Biochimica et biophysica acta.

[33]  Mojca Pavlin,et al.  Dependence of induced transmembrane potential on cell density, arrangement, and cell position inside a cell system , 2002, IEEE Transactions on Biomedical Engineering.

[34]  M J Jaroszeski,et al.  In vivo antitumor effects of electrochemotherapy in a hepatoma model. , 1997, Biochimica et biophysica acta.

[35]  S. Hagness,et al.  Quantification of electroporative uptake kinetics and electric field heterogeneity effects in cells. , 2008, Biophysical journal.

[36]  D. Miklavcic,et al.  Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. , 1998, British Journal of Cancer.

[37]  Deepak Dhar,et al.  Electric field of a six-needle array electrode used in drug and DNA delivery in vivo: analytical versus numerical solution , 2003, IEEE Transactions on Biomedical Engineering.

[38]  Damijan Miklavcic,et al.  Finite-element modeling of needle electrodes in tissue from the perspective of frequent model computation , 2003, IEEE Transactions on Biomedical Engineering.

[39]  R. Barr,et al.  Electric Fields in Tumors Exposed to External Voltage Sources: Implication for Electric Field-Mediated Drug and Gene Delivery , 2006, Annals of Biomedical Engineering.

[40]  James C. Weaver,et al.  Feasibility of an Electrode-Reservoir Device for Transdermal Drug Delivery by Noninvasive Skin Electroporation , 2007, IEEE Transactions on Biomedical Engineering.

[41]  N. Nakatsuji,et al.  In vivo transfection of testicular germ cells and transgenesis by using the mitochondrially localized jellyfish fluorescent protein gene , 2000, FEBS letters.

[42]  M. Bureau,et al.  High-efficiency gene transfer into skeletal muscle mediated by electric pulses. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[43]  D Miklavcic,et al.  Calculation of the electrical parameters in electrochemotherapy of solid tumours in mice , 1998, Comput. Biol. Medicine.

[44]  U. Pliquett,et al.  Joule heating during solid tissue electroporation , 2003, Medical and Biological Engineering and Computing.

[45]  M. Jaroszeski,et al.  Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode , 2007, Gene Therapy.