pyrimidinones and Coronary-Restenosis

This work aims to demonstrate the possibility to fabricate ultra-thin polymeric films loaded with an anti-restenotic drug and capable of tunable drug release kinetics for the local treatment of restenosis. Vascular nanopatches are composed of a poly(lactic acid) supporting membrane (thickness: ~250 nm) on which 20 polyelectrolyte bilayers (overall thickness: ~70 nm) are alternatively deposited. The anti-restenotic drug is embedded in the middle of the polyelectrolyte structure, and released by diffusion mechanisms. Nanofilm fabrication procedure and detailed morphological characterization are reported here. Barium titanate nanoparticles (showing piezoelectric properties) are included in the polymeric support and their role is investigated in terms of influence on nanofilm morphology, drug release kinetics, and cell response. Results show an efficient drug release from the polyelectrolyte structure in phosphate-buffered saline, and a clear antiproliferative effect on human smooth muscle cells, which are responsible for restenosis. In addition, preliminary evidences of ultrasound-mediated modulation of drug release kinetics are reported, thus evaluating the influence of barium titanate nanoparticles on the release mechanism. Such data were integrated with quantitative piezoelectric and thermal measurements. These results open new avenues for a fine control of local therapies based on smart responsive materials.

Topics: Barium Compounds; Cardiovascular Agents; Cell Adhesion; Cells, Cultured; Coronary Restenosis; Drug Carriers; Drug Delivery Systems; Humans; Lactic Acid; Muscle, Smooth, Vascular; Nanoparticles; Nanostructures; Polyesters; Polymers; Pyridines; Pyrimidinones; Titanium; Ultrasonics

The preventive effect of pemirolast against restenosis after coronary stent placement was evaluated.. Eighty-four patients with 89 de novo lesions who underwent successful coronary stenting were assigned to the pemirolast group(40 patients, 45 lesions) and the control group(44 patients, 44 lesions). Administration of pemirolast(20 mg/day) was initiated from the next morning after stenting and continued for 6 months of follow-up. Quantitative coronary angiography was performed immediately after stenting and at follow-up. Angiographic restenosis was defined as diameter stenosis > or = 50% at follow-up. Intravascular ultrasound study conducted at follow-up angiography was used to measure vessel cross-sectional area(CSA), stent CSA, lumen CSA, neointima CSA(stent CSA--lumen CSA), and percentage neointima CSA(neointima CSA/stent CSA x 100%) at the minimal lumen site.. There were no significant differences in baseline characteristics between the two groups. Restenosis rate was significantly lower in the pemirolast group than in the control group(15.0% vs 34.1% of patients, 13.3% vs 34.1% of lesions, p < 0.05, respectively). The intravascular ultrasound study at follow-up(36 lesions in the pemirolast group, 33 in the control group) found no significant differences in vessel CSA and stent CSA between the two groups(17.3 +/- 2.2 vs 16.8 +/- 2.4 mm2, 8.6 +/- 1.9 vs 8.4 +/- 1.7 mm2, respectively). However, lumen CSA was significantly larger in the pemirolast group than in the control group(5.5 +/- 1.3 vs 4.4 +/- 1.1 mm2, p < 0.05). Moreover, neointima CSA and percentage neointima CSA were significantly smaller in the pemirolast group(3.1 +/- 1.1 vs 4.0 +/- 1.2 mm2, p < 0.05 and 36.2 +/- 15.9% vs 47.4 +/- 15.6%, p < 0.01).. Pemirolast has a preventive effect against restenosis after stent placement, possibly by inhibiting neointimal hyperplasia.

Topics: Aged; Angioplasty, Balloon, Coronary; Anti-Allergic Agents; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Female; Humans; Male; Middle Aged; Pyridines; Pyrimidinones; Stents; Ultrasonography, Interventional