Paclitaxel/sirolimus combination coated drug-eluting stent: in vitro and in vivo drug release studies
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Published on: September 20, 2011
Xiaodong Ma1, Shizu Oyamada, Fan Gao
1Biomedical Engineering and Biotechnology Doctoral Program, University of Massachusetts, Lowell, MA 01854, USA.
Abstract:
Paclitaxel and sirolimus are the two major drugs for the treatment of coronary arterial disease in current drug-eluting stents. The two drugs can effectively inhibit the in-stent restenosis through their independent pathways and show synergistic effect in preventing tumor tissue growth. We hypothesize that the combination of the two drugs in a drug-eluting stent (DES) can also effectively suppress the neointima growth in the stented artery. The present work was focused on the investigation of paclitaxel/sirolimus combination release profiles from a novel biodegradable polymer (poly (D, L-lactide-co-glycolide)/amorphous calcium phosphate, PLGA/ACP) coated stent both in vitro and in vivo. For the in vitro, the drug releasing profiles were characterized by measuring the drug concentration in a drug release medium (Dulbecco's phosphate buffered saline, DPBS, pH 7.4) at predetermined time points. For the in vivo, a rat aorta stenting model was employed. The results showed that both paclitaxel and sirolimus had a two-phase release profile both in vitro and in vivo, which is similar to the drug release profile of their individual coated DESs, and there is no evident of interference between two drugs. The data suggest that paclitaxel and sirolimus can be combined pharmacokinetically in a DES for the treatment of coronary arterial diseases.
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