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.

We introduce the use of block copolymer membranes for an emerging application, “drug capture”. The polymer is incorporated in a new class of biomedical devices, referred to as ChemoFilter, which is an image-guided temporarily deployable endovascular device designed to increase the efficacy of chemotherapy-based cancer treatment. We show that block copolymer membranes consisting of functional sulfonated polystyrene end blocks and a structural polyethylene middle block (S-SES) are capable of capturing doxorubicin, a chemotherapy drug. We focus on the relationship between morphology of the membrane in the ChemoFilter device and efficacy of doxorubicin capture measured in vitro. Using small-angle X-ray scattering and cryogenic scanning transmission electron microscopy, we discovered that rapid doxorubicin capture is associated with the presence of water-rich channels in the lamellar-forming S-SES membranes in aqueous environment.

Background and purpose Despite evidence regarding risk factors for brain arteriovenous malformation (bAVM)-associated spontaneous intracranial hemorrhage (ICH), few data exist describing the spectrum of clinical outcomes that bAVM-associated ICH may manifest. This study aimed to identify the demographical, clinical, and bAVM anatomical variables associated with ICH volume and the presence of intraventricular hemorrhage (IVH) of ruptured bAVMs, two indicators of worse clinical outcome, to help better predict outcome for unruptured bAVMs. Methods Computed tomography images ( n = 169) of patients with ruptured bAVM in a prospectively maintained institutional database were retrospectively reviewed to calculate ICH volume and the presence or absence of IVH. Demographic, clinical, and bAVM characteristics information was summarized and analyzed with univariable and multivariable regression models to identify the associations of these features with ICH volume and the presence of IVH. Results Patient sex, exclusively deep venous drainage, and lobar location were associated with ICH volume in univariable analysis; exclusively deep venous drainage remained significant in multivariable analysis (PI = 0.33, 95% CI: 0.21–0.52, p < 0.001). Exclusively deep venous drainage, multiple feeding arteries, and venous stenosis were associated with IVH in univariable analysis; exclusively deep venous drainage (OR = 7.27, 95% CI: 1.94–27.29, p = 0.003) remained significant in multivariable analysis. Conclusions Variables associated with ICH volume and the presence of IVH in ruptured bAVMs were evaluated and identified. They impart information that may help predict the clinical outcome of unruptured bAVM, in turn aiding clinicians in treatment planning.

To determine if endovascular chemofiltration with an ionic device (ChemoFilter [CF]) can be used to reduce systemic exposure and off-target biodistribution of doxorubicin (DOX) during hepatic intra-arterial chemotherapy (IAC) in a preclinical model. Materials and Methods:Hepatic IAC infusions were performed in six pigs with normal livers. Animals underwent two 10-minute intraarterial infusions of DOX (200 mg) into the common hepatic artery. Both the treatment group and the control group received initial IAC at 0 minutes and a second dose at 200 minutes. Prior to the second dose, CF devices were deployed in and adjacent to the hepatic venous outflow tract of treatment animals. Systemic exposure to DOX was monitored via blood samples taken during IAC procedures. After euthanasia, organ tissue DOX concentrations were analyzed. Alterations in systemic DOX exposure and biodistribution were compared by using one-tailed t tests.Results: CF devices were well tolerated, and no hemodynamic, thrombotic, or immunologic complications were observed. Animals treated with a CF device had a significant reduction in systemic exposure when compared with systemic exposure in the control group (P ,.009). Treatment with a CF device caused a significant decrease in peak DOX concentration (31%, P ,.01) and increased the time to maximum concentration (P ,.03). Tissue analysis was used to confirm significant reduction in DOX accumulation in the heart and kidneys (P ,.001 and P ,.022, respectively). Mean tissue concentrations in the heart, kidneys, and liver of animals treated with CF compared with those in control animals were 14.2 mg/g 6 1.9 (standard deviation) versus 26.0 mg/g 6 1.8, 46.4 mg/g 6 4.6 versus 172.6 mg/g 6 40.2, and 217.0 mg/g 6 5.1 versus 236.8 mg/g 6 9.0, respectively. Fluorescence imaging was used to confirm in vivo DOX binding to CF devices. Conclusion:Reduced systemic exposure and heart bioaccumulation of DOX during local-regional chemotherapy to the liver can be achieved through in situ adsorption by minimally invasive image-guided CF devices.