Development of filter device to limit systemic toxicity from doxorubicin chemotherapy: DNA ChemoFilter
Objective: ChemoFilter is a new class of image-guided temporarily deployable, endovascular catheter based medical device that selectively filters chemotherapeutic agents from the bloodstream to limit systemic toxicities. We report a novel method to filter doxorubicin in blood using genomic DNA as resin.
Materials and Methods: DNA binding experiments were performed in vitro with doxorubicin in PBS solution and porcine serum. Genomic DNA was used for binding experiments, with the DNA either free in solutions or with the DNA encapsulated in packets made with nylon or polyester mesh. Optimum concentration of genomic DNA to filter 50 mg doxorubicin in solution was determined. We then compared the kinetics of filtering doxorubicin by genomic DNA as compared to our previously published ion exchange resin based ChemoFilter.
Results: Doxorubicin concentration was reduced by over 90% within 1 minute with free DNA in PBS and porcine serum. With packaged DNA, doxorubicin concentration was reduced by 50% within 5 minutes in PBS, and 90% within 1 minute in porcine Serum.
Doxorubicin filtering kinetics between DNA and the ion exchange resin Dowex were compared in each binding experiments and the DNA displayed more rapid kinetics in all situations.
Conclusion: We describe a new version of ChemoFilter that uses DNA as the binding agent for DNA binding drugs. DNA ChemoFilter allows selective filtration of DNA binding chemotherapeutic agents and demonstrates more rapid kinetics than previously described ion exchange version of ChemoFilter.