Publications by authors named "Douglas W Brown"

3 Publications

  • Page 1 of 1

Real-time impedance feedback to enhance cutaneous gene electrotransfer in a murine skin model.

Bioelectrochemistry 2021 Jul 13;142:107885. Epub 2021 Jul 13.

Department of Chemical, Biological, and Materials Engineering, University of South Florida, 4202 E. Fowler Ave ENG 030, Tampa, FL 33620, USA; Center for Molecular Delivery at USF, University of South Florida, 4202 E. Fowler Ave ENG 030, Tampa, FL 33620, USA; Department of Medical Engineering, University of South Florida, 4202 E. Fowler Avenue ENG 030, Tampa, FL 33620, USA. Electronic address:

Electric field mediated gene delivery methods have the ability to efficiently transfect cells in vivo with an excellent safety profile. The method has historically used a fixed number of electric pulses with identical characteristics in induce delivery. Electrical treatment does not typically compensate for subject-to-subject variation and other differences. This study was designed to investigate if delivery/expression could be increased using a novel electropulsation method that compensated for variation using real-time electrical impedance measurements. The method involved delivering plasmid DNA encoding luciferase to murine skin. Tissue impedance in a 1-3 KHz range was measured before electric pulses were applied. Impedance was also measured after each successive pulse. Pulsation was stopped when impedance values were reduced by either 80% or 95% relative to prepulse values. Standard/fixed pulsing parameters were also used for comparison. The results indicated that up to 15-fold increases in luciferase expression could be obtained when electrical treatment was ceased based upon impedance reductions. Furthermore, peak expression levels of all treatment groups pulsed using the novel pulsing method were statistically higher than those that employed standard pulsing. These results strongly suggest that applying pulses until a defined impedance-based endpoint results in higher expression.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107885DOI Listing
July 2021

Development of an adaptive electroporation system for intratumoral plasmid DNA delivery.

Bioelectrochemistry 2018 Aug 9;122:191-198. Epub 2018 Apr 9.

OncoSec Medical Incorporated, 5820 Nancy Ridge Drive, San Diego, CA, USA. Electronic address:

Intratumoral electroporation of plasmid DNA encoding the proinflammatory cytokine interleukin 12 promotes innate and adaptive immune responses correlating with anti-tumor effects. Clinical electroporation conditions are fixed parameters optimized in preclinical tumors, which consist of cells implanted into skin. These conditions have little translatability to clinically relevant tumors, as implanted models cannot capture the heterogeneity encountered in genetically engineered mouse models or clinical tumors. Variables affecting treatment outcome include tumor size, degree of vascularization, fibrosis, and necrosis, which can result in suboptimal gene transfer and variable therapeutic outcomes. To address this, a feedback controlled electroporation generator was developed, which is capable of assessing the electrochemical properties of tissue in real time. Determination of these properties is accomplished by impedance spectroscopy and equivalent circuit model parameter estimation. Model parameters that estimate electrical properties of cell membranes are used to adjust electroporation parameters for each applied pulse. Studies performed in syngeneic colon carcinoma tumors (MC38) and spontaneous mammary tumors (MMTV-PyVT) demonstrated feedback-based electroporation is capable of achieving maximum expression of reporter genes with significantly less variability and applied energy. These findings represent an advancement to the practice of gene electro-transfer, as reducing variability and retaining transfected cell viability is paramount to treatment success.
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http://dx.doi.org/10.1016/j.bioelechem.2018.04.005DOI Listing
August 2018

Impedance spectroscopy as an indicator for successful in vivo electric field mediated gene delivery in a murine model.

Bioelectrochemistry 2017 Jun 27;115:33-40. Epub 2017 Jan 27.

Department of Chemical and Biomedical Engineering, University of South Florida, 4202 E. Fowler Ave. ENB 118, Tampa, FL 33620, USA; Center for Molecular Delivery at USF, University of South Florida, 4202 E. Fowler Ave. ENB 118, Tampa, FL 33620, USA.

In vivo gene electro transfer technology has been very successful both in animal models and in clinical trials over the past 20years. However, variable transfection efficiencies can produce inconsistent outcomes. This can be due to differences in tissue architecture and/or chemical composition which may effectively create unique biological environments from subject to subject that may respond differently to the identical electric pulses. This study investigates the integration of impedance spectroscopy into the gene electro transfer process to measure murine skin impedance spectra before, during (after pulse delivery), and after gene electro transfer pulse application to determine if changes in impedance correlate with reporter gene expression. Both post-treatment impedance spectra and gene expression were dependent upon the applied electric field strength. These results indicate that alterations in tissue impedance produced by the applied electric field represent an excellent parameter to predict degrees of transfection and gene expression. These results could ultimately be used to alter pulsing parameters in order to optimize delivery/expression.
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http://dx.doi.org/10.1016/j.bioelechem.2017.01.004DOI Listing
June 2017
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