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Published on: October 26, 2016
Harnessing the pleiotropic effects of atorvastatin-fenofibrate combination for cardiovascular stents
Purandhi Roopmani1, Uma Maheswari Krishnan1
1Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur 613 401, Tamil Nadu, India.
Insights
Combining atorvastatin and fenofibrate in drug-eluting stents shows promise. This dual-drug coating inhibits thrombus formation and inflammation while promoting endothelialization for better stent performance.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Pharmacology
Background:
- Atorvastatin and fenofibrate are established lipid-lowering drugs with beneficial pleiotropic effects.
- These effects include anti-inflammatory and vasodilatory actions, potentially addressing limitations of current drug-eluting stents like late stent thrombosis and delayed endothelialization.
- The combination of atorvastatin and fenofibrate has not been previously investigated for therapeutic coatings on drug-eluting stents.
Purpose of the Study:
- To investigate the potential of an atorvastatin-fenofibrate combination loaded in a biodegradable poly(l-lactide-co-caprolactone) film for drug-eluting stent applications.
- To evaluate the combination's effects on inhibiting thrombus formation and macrophage activation.
- To assess the impact on smooth muscle cell and endothelial cell proliferation.
Main Methods:
- Fabrication and characterization of dual drug-loaded biodegradable polymer films using spectroscopy and calorimetry.
- In vitro assessment of the drug combination's effect on smooth muscle cell and endothelial cell proliferation.
- Evaluation of anti-thrombogenic and anti-inflammatory properties by measuring platelet and macrophage adhesion and activation.
Main Results:
- The atorvastatin-fenofibrate combination effectively retarded smooth muscle cell proliferation but not endothelial cell proliferation, favoring re-endothelialization.
- Dual drug-loaded films demonstrated significant reductions in platelet and macrophage adhesion and activation, indicating potent anti-thrombogenic and anti-inflammatory effects.
- The observed pleiotropic effects are potentially linked to nitric oxide synthase activation in endothelial cells, with no alteration in mTOR levels.
Conclusions:
- The atorvastatin-fenofibrate combination loaded in a biodegradable polymer shows significant potential as a therapeutic coating for drug-eluting stents.
- The combination effectively inhibits thrombosis and inflammation while promoting endothelialization, addressing key limitations of current stent technologies.
- Further research into this dual-drug approach could lead to improved cardiovascular device performance and patient outcomes.
Abstract:
Atorvastatin and fenofibrate have been conventionally employed as lipid-lowering agents. They also exhibit beneficial effects in the treatment of endothelial dysfunction, oxidative stress and vascular inflammation due to their pleiotropic effects that include vasodilatory and anti-inflammatory effects. These pleiotropic effects may serve to overcome the drawbacks of late stent thrombosis and delayed endothelialization that plague conventional drug eluting stents. However, the combination has not been explored yet as therapeutic coatings in drug eluting stents. The present study aims to investigate the potential of atorvastatin-fenofibrate combination loaded in a biodegradable poly(l-lactide-co-caprolactone) polymer film to inhibit thrombus formation and macrophage activation apart from exploring their effect on the proliferation of smooth muscle cells and endothelial cells. The dual drug-loaded polymer films were characterized by spectroscopy and calorimetry. In vitro studies revealed that the combination effectively retarded the proliferation of only smooth muscle cells but not the endothelial cells which augers well for stent applications where rapid re-endothelialization is preferred. Further, the dual drug-loaded films exhibited a marked decrease in the adhesion and activation of platelets and macrophages revealing the potent anti-thrombogenic and anti-inflammatory effects of the combination. The pleiotropic effects of the combination may be attributed to their ability to activate nitric oxide synthase in endothelial cells while mTOR levels remained unaltered by the combination.
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