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

Mariam S. Aboian, Jay F. Yu, Ayushi Gautam, Chia Hung Sze, Jeffrey K. Yang, Jonathan Chan, Prasheel V. Lillaney, Caroline D. Jordan, Hee Jeung Oh, David M. Wilson, Anand S. Patel, Mark W. Wilson, Steven W. Hetts

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Article number98
JournalBiomedical Microdevices
Volume18
Issue number6
DOIs
StatePublished - Dec 1 2016

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Molecular Biology

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    Aboian, M. S., Yu, J. F., Gautam, A., Sze, C. H., Yang, J. K., Chan, J., Lillaney, P. V., Jordan, C. D., Oh, H. J., Wilson, D. M., Patel, A. S., Wilson, M. W., & Hetts, S. W. (2016). In vitro clearance of doxorubicin with a DNA-based filtration device designed for intravascular use with intra-arterial chemotherapy. Biomedical Microdevices, 18(6), [98]. https://doi.org/10.1007/s10544-016-0124-5