Localized arterial wall drug delivery from a polymer-coated removable metallic stent. Kinetics, distribution, and bioactivity of forskolin
| Autor: | Frank Litvack, Eldad Rechavia, Vishva Dev, Thomas L. Dr. Lambert, N L Eigler, James S. Forrester |
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| Rok vydání: | 1994 |
| Předmět: |
Time Factors
medicine.medical_treatment Polyurethanes Vasodilation chemistry.chemical_compound Drug Delivery Systems Restenosis Physiology (medical) Alloys Colforsin Animals Medicine Tissue Distribution Carotid Artery Thrombosis Forskolin business.industry Stent Equipment Design medicine.disease Carotid Arteries medicine.anatomical_structure chemistry Cerebrovascular Circulation Anesthesia Drug delivery Stents Vascular Resistance Rabbits Cardiology and Cardiovascular Medicine business Half-Life Artery Biomedical engineering |
| Zdroj: | Circulation. 90:1003-1011 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.90.2.1003 |
| Popis: | BACKGROUND Coronary stenting is associated with two major complications: subacute thrombosis and neointimal proliferation resulting in restenosis. Our hypothesis is that the biocompatibility of metallic stents can be improved by coating with a polymer membrane that delivers agents that favorably modify the local arterial microenvironment. This study evaluates the kinetics, distribution, and bioactivity of the model drug forskolin delivered to the local arterial wall by a polyurethane-coated removable metallic stent. METHODS AND RESULTS Stents were used in rabbit carotid arteries (n = 20) for as long as 24 hours. The quantity of forskolin bound to the stent decreased exponentially with a half-life of 5.8 hours. Blood concentrations peaked at 140 +/- 39 pg/microL at 4 hours. The adjacent arterial media contained 60 +/- 39 ng/mg, which was 380- and 460-fold greater than the contralateral carotid media and the systemic blood, respectively (P < .0001). Media forskolin concentrations declined exponentially over time with a tissue half-life of 5.0 hours. Drug distributed throughout the vessel wall with decreasing gradients in the radial and axial dimensions consistent with a diffusion process. Removal of the stent was associated with a 100-fold decline in media forskolin concentration within 2 hours. Forskolin release was associated with a sustained 92% increase in carotid blood flow and a 60% decrease in local arterial resistance compared with coated control stents (P < .005). In another set of rabbits (n = 14) using a carotid crush injury, flow-reduction model, forskolin prolonged the time to flow variation and occlusion by 12-fold compared with the use of bare metal stents and 5-fold compared with the use of polyurethane-coated stents (P < .0001). CONCLUSIONS A polymer-coated metallic stent can deliver forskolin to the local arterial wall in high concentrations relative to the blood or other tissues. High local drug concentrations are dependent on maintaining stent-to-tissue gradients. The delivered drug is biologically active, demonstrating vasodilating and antiplatelet properties. |
| Databáze: | OpenAIRE |
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