title: In vitro clearance of doxorubicin with a DNA-based filtration device designed for intravascular use with intra-arterial chemotherapy.
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.
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Mariam S
authors: MS
authors: Aboian
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Jay F
authors: JF
authors: Yu
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Ayushi
authors: A
authors: Gautam
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Chia-Hung
authors: CH
authors: Sze
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Jeffrey K
authors: JK
authors: Yang
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Jonathan
authors: J
authors: Chan
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Prasheel V
authors: PV
authors: Lillaney
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Caroline D
authors: CD
authors: Jordan
authors: Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, 94720, USA.
authors: Hee-Jeung
authors: HJ
authors: Oh
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: David M
authors: DM
authors: Wilson
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Anand S
authors: AS
authors: Patel
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA.
authors: Mark W
authors: MW
authors: Wilson
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Suite 350, Room 320, San Francisco, CA, 94107-5705, USA. steven.hetts@ucsf.edu.
authors: Steven W
authors: SW
authors: Hetts
mesh_terms: D000818:Animals; D001158:Arteries; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification* / Q000627:therapeutic use; D004867:Equipment Design; D005240:Feasibility Studies; D005374:Filtration / Q000295:instrumentation*; D007700:Kinetics; D013552:Swine
chemical_list: D004317:Doxorubicin; D004247:DNA
keywords: Chemotherapy; Detoxification; Endovascular devices