The present invention provides compositions comprising an anti-angiogenic factor, and a polymeric carrier. Representative examples of anti-angiogenic factors include Anti-Invasive Factor, Retinoic acids and derivatives thereof, and paclitaxel. Also provided are methods for embolizing blood vessels, and eliminating biliary, urethral, esophageal, and tracheal/bronchial obstructions.

Anti-angiogenic compositions and methods of use

Normal coronary arteries in dogs, atherosclerotic human coronary arteries at autopsy, and rabbit iliac arteries with experimental atherosclerosis were subjected to angioplasty and studied histologically or by electron microscopy. The studies showed desquamation of endothelium, deposition of platelets in the area of angioplasty, and splitting of atheromatous plaques frequently down to the internal elastic membrane. Human coronary arteries studied at post-mortem after successful angioplasty also have demonstrated splitting of the atheromatous plaque at its weakest point. Compression of atheromatous material from the plaque has not been demonstrated experimentally. The mechanism of angioplasty is complex. As the angioplasty balloon expands, splitting of the atheromatous plaque occurs at its weakest, thinnest point. The media and adventitia of the artery are then stretched, producing an enlarged lumen and increased blood flow. Splitting of the atherosclerotic plaque explains the angiographic appearance frequently seen after angioplasty--a separate column of angiographic dye or a small radiolucent filling defect in the area of successful angioplasty.

The mechanism of transluminal angioplasty.

Subacute thrombosis is a significant problem after stent insertion. Use of polymer-coated stents impregnated with drugs could reduce its incidence. We investigated the binding and elution kinetics and antithrombotic efficacy of three agents passively adsorbed onto commercially available polymer-coated stainless steel stents: (1) urokinase (UK), (2) an antirabbit platelt glycoprotein IIb/IIIa receptor antibody (AZ1), and (3) a UK-AZ1 chemical conjugate (C). Stent wire segments were immersed in125Iodine-radiolabeled drug (0.1 or 1 g/L). Binding increased with immersion time and drug concentration (Fig. 1). Significantly more AZ1 or C than UK bound at both concentrations (p<0.01). Elution was assessed by perfusing stents with phosphate-saline buffer and 1% serum albumin. Anti-thrombotic efficacy was assessed by perfusing stents with111Indium-labeled rabbit platelets. The results are shown in Tables 1 and 2. Significantly more AZ1 or C than UK remained bound to stents at all times (p<0.01). Stents with no bound drugs displayed significantly greater platelet adhesion (441±28×103) than stents with AZ1 or C (p<0.01). We conclude that platelet-targeted fibrinolytic agents can be passively bound to polymer-coated stents and are well retained even after prolonged continuous perfusion. Such agents retain their efficacy and reduce platelet deposition on stents more effectively than antiplatelet agents or nontargeted fibrinolytics alone. These agents may thus reduce stent-related thrombosis and require furtherin vivo evaluation.

In vitro development of the nonthrombogenic stent

Atherosclerotic cardiovascular disease remains the leading cause of death in industrialized countries. Medical treatment has been largely unsuccessful in altering its course. Surgery is an effective treatment in selected cases but carries with it significant morbidity. Percutaneous balloon angioplasty has been developed as an alternative treatment. Since its introduction by Dotter [1] in peripheral arteries, and Gruntzig [2] in coronary arteries, angioplasty has seen a dramatic rise in popularity. In the USA alone, over 200000 coronary angioplasties will be performed in 1990 [3]. However, the success of PTCA has been limited by two major complications: acute vessel closure and late restenosis.

Bioabsorbable Endovascular Stent Prostheses

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Bioabsorbable Endovascular Stent Prostheses