Patent 8738125: Devices and methods for delivering molecules to the heart with electric fields
A device and related methodologies to deliver molecules to the cells that comprise any tissues. The invention includes a catheter-based electrode and methods for its use for the delivery of molecules to cardiac tissue, blood vessels, other tissues/organs that can be accessed through a luminal tissue, and luminal tissues. The invention is also a non-catheter based electrode for performing the same functions. In certain embodiments the electrode utilizes a segmented electrode array wherein each electrode is separately addressable by a source of electricity.
An injection and electroporation delivery device according to the invention can be fitted on the tip of a catheter to access and treat tissues that can be accessed using tissues that have a lumen. The heart provides an example of a tissue can be accessed using a catheter with this device on the tip through any number of blood vessels that lead to it. Similarly, kidney, lung, pancreas, liver, gall bladder, urinary bladder, prostate, and stomach can be accessed and treated using the device mounted on the tip of a catheter. The diameter of the device can be tailored to any size that is suitable for accessing the tissue of interest.
In addition, the device can be used to treat the luminal pathway itself. One advantage of the system described herein is that it does not rely on balloon-based systems, as do many of the catheter based electrodes for treating vessels. Moreover, the device can be used in a non-expandable format.
Treatment of the tissue site by localized delivery of the therapeutic agent coupled with focused delivery of the electroporation signal facilitates selective application of the treatment to the target tissue sought to be treated. In this manner surrounding tissue is spared the adverse effects of treatment while the targeted tissue receives enhanced more optimal levels of the agent.
lasmid DNA-based gene transfer is attractive because it eliminates the need for a biological vector. Application of plasmid DNA-based gene transfer has been handicapped by the lack of efficient and/or effective delivery methods. When compared to viral delivery, the advantages of plasmid DNA-based gene transfer include reduced potential for immunogenicity, integration into the genome, and environmental spread. One method that has emerged as a means to facilitate delivery of plasmid DNA is in vivo electroporation or electropermeabilization.
BACKGROUND OF THE INVENTION
Electroporation (“EP”) originated for in vitro transfection (Neumann et al., 1982) and over the past 25 years has become a standard laboratory method. The administration of electric fields at specific pulse conditions increases cell membrane permeability, which allows uptake of molecules through the cell membrane. The initial demonstration of in vivo electroporation was the delivery of chemotherapeutic agents to solid tumors (Okino et al. 1991). In the mid to late 1990's, the effectiveness of this approach for drug delivery was demonstrated in a variety of different tumors in animals and humans (Gotheif et al, 2003). This technique was then tested for enhanced plasmid DNA delivery (Holler et al., 1996; Nishi et al, 1996). In vivo electroporation is theoretically applicable to all tissues tested. A principal issue limiting the use of in vivo electroporation has been the accessibility of the particular tissue for the application of the electric field. The use of in vivo electroporation for plasmid DNA deliver has seen tremendous growth, including the initiation of the first clinical trials.
My conclusion:
As anyone can see, the invention and the use of electroporation has been years in the making and now doctors are ready to apply it to patients. There has been enough research done on the matter which means that what’s really needed is to comply with FDA regulations in order to get approval. Its background in past clinical usage can explain why there is no need for large patient trials.
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