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      In vitro clearance of doxorubicin with a DNA-based filtration device designed for intravascular use with intra-arterial chemotherapy

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          Abstract

          To report a novel method using immobilized DNA within mesh to sequester drugs that have intrinsic DNA binding characteristics directly from flowing blood. DNA binding experiments were carried out in vitro with doxorubicin in saline (PBS solution), porcine serum, and porcine blood. Genomic DNA was used to identify the concentration of DNA that shows optimum binding clearance of doxorubicin from solution. Doxorubicin binding kinetics by DNA enclosed within porous mesh bags was evaluated. Flow model simulating blood flow in the inferior vena cava was used to determine in vitro binding kinetics between doxorubicin and DNA. The kinetics of doxorubicin binding to free DNA is dose-dependent and rapid, with 82–96 % decrease in drug concentration from physiologic solutions within 1 min of reaction time. DNA demonstrates faster binding kinetics by doxorubicin as compared to polystyrene resins that use an ion exchange mechanism. DNA contained within mesh yields an approximately 70 % decrease in doxorubicin concentration from solution within 5 min. In the IVC flow model, there is a 70 % drop in doxorubicin concentration at 60 min. A DNA-containing ChemoFilter device can rapidly clear clinical doses of doxorubicin from a flow model in simple and complex physiological solutions, thereby suggesting a novel approach to reduce the toxicity of DNA-binding drugs.

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          Author and article information

          Journal
          100887374
          31971
          Biomed Microdevices
          Biomed Microdevices
          Biomedical microdevices
          1387-2176
          1572-8781
          8 April 2017
          December 2016
          01 December 2017
          : 18
          : 6
          : 98
          Affiliations
          [1 ]Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA 94107-5705, USA
          [2 ]Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA 94720, USA
          Article
          PMC5441460 PMC5441460 5441460 nihpa863558
          10.1007/s10544-016-0124-5
          5441460
          27778226
          Categories
          Article

          Endovascular devices, Chemotherapy, Detoxification

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