sirolimus and iopromide

Percutaneous transluminal angioplasty revolutionized coronary and peripheral revascularization. However, it is always accompanied by major drawbacks such as elastic recoil and neointimal hyperplasia. Percutaneous transluminal angioplasty along with bare metal stents reduced elastic recoil, but in-stent restenosis (ISR) and peripheral artery stenting remain problems. Drug-eluting stents addressed the issue of ISR, but late stent thrombosis and delayed endothelialization, along with longer dual antiplatelet therapy, are of concern. Non-stent-based delivery such as drug-coated balloons (DCBs) that can deliver drugs to inhibit ISR or to de novo lesions, are emerging at a rapid pace. DCBs carry an active drug and a nonpolymeric carrier molecule or excipient that enhance the bioavailability of the drug to the vessel wall. Preliminary studies of paclitaxel show sustained delivery is not required to inhibit proliferation of vascular smooth muscle cells, which leds to the development and evolution of DCBs. Recent clinical trials have been successful in mitigating ISR in coronary and peripheral arteries, but not in de novo lesions of coronary arteries. Clinical studies, although limited to date, show a promising future for DCBs.

Topics: Angioplasty, Balloon; Drug-Eluting Stents; Humans; Iohexol; Paclitaxel; Sirolimus; Vascular Access Devices

To evaluate the potential of in vivo dynamic contrast-enhanced micro-computed tomography (DCE micro-CT) for the assessment of antiangiogenic drug therapy response of mice with mammary carcinoma.. 20 female mice with implanted MCF7 tumours were split into control group and therapy group treated with a known effective antiangiogenic drug. All mice underwent DCE micro-CT for the 3D analysis of functional parameters (relative blood volume [rBV], vascular permeability [K], area under the time-enhancement curve [AUC]) and morphology. All parameters were determined for total, peripheral and central tumour volumes of interest (VOIs). Immunohistochemistry was performed to characterise tumour vascularisation. 3D dose distributions were determined.. The mean AUCs were significantly lower in therapy with P values of 0.012, 0.007 and 0.023 for total, peripheral and central tumour VOIs. K and rBV showed significant differences for the peripheral (P(per)(K) = 0.032, P(per) (rBV) = 0.029), but not for the total and central tumour VOIs (P(total)(K) = 0.108, P(central)(K) = 0.246, P(total) (rBV) = 0.093, P(central) (rBV) = 0.136). Mean tumour volume was significantly smaller in therapy (P (in vivo) = 0.001, P (ex vivo) = 0.005). Histology revealed greater vascularisation in the controls and central tumour necrosis. Doses ranged from 150 to 300 mGy.. This study indicates the great potential of DCE micro-CT for early in vivo assessment of antiangiogenic drug therapy response.. Dynamic contrast enhanced micro-CT (computed tomography) is a new experimental laboratory technique. DCE micro-CT allows early in vivo assessment of antiangiogenic drug therapy response. Pharmaceutical drugs can be tested before translation to clinical practice. Both morphological and functional parameters can be obtained using DCE micro-CT. Antiangiogenic effects can be visualised with DCE micro-CT.

Topics: Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Contrast Media; Everolimus; Female; Imaging, Three-Dimensional; Iohexol; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Reproducibility of Results; Sensitivity and Specificity; Sirolimus; Tomography, X-Ray Computed; Treatment Outcome

EPC and hCASMC play an important role in the pathogenesis of restenosis and stent thrombosis. Drug-coated balloon catheters exert a local, short-term application of antiproliferative agents. This study investigates the time-dependent influence on growth and motility of paclitaxel and sirolimus alone and combined with the coating additive iopromide on EPC and hCASMC.. Treatment of cultured human EPC and hCASMC with paclitaxel and sirolimus 1.5 and 15 µM for three seconds, three minutes and 24 hours, alone or combined with iopromide 0.197 M, resulted in a concentration- and time- dependent inhibition of proliferation and of migration. Paclitaxel and sirolimus increase apoptosis in either cell type. However, the effects of paclitaxel and sirolimus differed between the cell types: short-term exposure with paclitaxel leads to stronger inhibition of cell-density and apoptosis of hCASMC compared to EPC. In comparison to paclitaxel, short-term incubation with sirolimus showed a more effective inhibition of cell-density and migration as well as increased apoptosis in EPC in contrast to hCASMC. The effects of paclitaxel and sirolimus were increased in combination with iopromide. Interestingly, the antiproliferative effect of the paclitaxel-iopromide formulation on hCASMC was more potent compared to its effect on EPC. Endothelialisation in a porcine coronary stent model was similar with drug-coated balloons and uncoated controls, whereas it was delayed with drug-eluting stents.. After short-term application, paclitaxel and sirolimus show differential, cell-specific effects on EPC and hCASMC. Iopromide used as a coating agent intensifies these effects.

Topics: Angioplasty, Balloon, Coronary; Animals; Apoptosis; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Vessels; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug-Eluting Stents; Endothelial Cells; Equipment Design; Humans; Iohexol; Models, Animal; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Paclitaxel; Sirolimus; Stem Cells; Sus scrofa; Time Factors