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Novel Method of Plasmid DNA Delivery to Mouse Bladder Urothelium by Electroporation
Published on: May 3, 2018
Integration of Electroporation in Urological Practice: Design and Evaluation of a New Transurethral Electrode
Rose Bryde Laursen1, Pernille Holst2, Thomas Eriksen2
1Department of Urology, Copenhagen University Hospital - Zealand University Hospital Roskilde; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.
Abstract:
Bladder tumors constitute a substantial health challenge, yet advances in the treatment have been few. Electroporation is the use of brief electric pulses that permeabilize cell membranes with the purpose of a direct cytotoxic effect (irreversible electroporation) or for drug and gene delivery into cells (reversible electroporation). In this study, calcium was used (calcium electroporation). The use of electroporation in uro-oncology has been limited due to a lack of suitable instruments. The study focuses on the design and clinical usability of a new transurethral electrode and its technical performance in pigs. This fixed-geometry electrode consists of two opposing arrays of three needles each. The central needle is offset from an imaginary line between the two outermost needles. This ensures uniform, square-shaped electric field distribution. The electrode is compatible with a transurethral resectoscope and is an interchangeable working element through which the telescope inserts. The external pulse generator connects to the handle. Locking mechanisms ensure alignment of the equipment during assembly. The suitability was assessed in healthy porcine bladders, which resemble the human and allow the use of similar instruments. Under general anesthesia, the resectoscope was inserted transurethrally. Calcium was injected into the bladder wall with an endoscopic needle, the electrode was inserted, and the needles were placed in the area injected with calcium. Electric pulses were applied (8 pulses, 100 µs, 5000 Hz, and 400 V corresponding to 1000 V/cm voltage to electrode distance ratio). Afterwards the instruments were retracted. The handling of the instruments closely mirrors established urological techniques. The positioning of the electrode was visually managed, and the pulse delivery equaled standard transurethral procedures. Pulses were delivered successfully. The transurethral use and performance of the new electrode in the bladder aligns with existing urological instruments and techniques, enabling seamless adaptation by urologists.
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