In vitro clearance of doxorubicin with a DNA-based filtration device designed for intravascular use with intra-arterial chemotherapy
| Autor: | Chia Hung Sze, Mark W. Wilson, Jonathan K.L. Chan, J. Yang, Caroline D. Jordan, Ayushi Gautam, David M. Wilson, Mariam Aboian, Jay F. Yu, Anand S. Patel, Prasheel Lillaney, Steven W. Hetts, Hee Jeung Oh |
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| Rok vydání: | 2016 |
| Předmět: |
Swine
medicine.medical_treatment Endovascular devices Kinetics Biomedical Engineering Bioengineering Cardiovascular Inferior vena cava Article 030218 nuclear medicine & medical imaging Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Chemotherapy Animals Doxorubicin Molecular Biology Cancer Materials Engineering Arteries DNA Equipment Design In vitro Receptor–ligand kinetics genomic DNA chemistry medicine.vein 5.1 Pharmaceuticals 030220 oncology & carcinogenesis Biophysics Feasibility Studies Development of treatments and therapeutic interventions Detoxification Filtration medicine.drug Biomedical engineering |
| Zdroj: | Biomedical microdevices, vol 18, iss 6 |
| ISSN: | 1572-8781 |
| Popis: | 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 1min 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 5min. In the IVC flow model, there is a 70% drop in doxorubicin concentration at 60min. 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. |
| Databáze: | OpenAIRE |
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