| Summary: | 博士 === 國立清華大學 === 化學工程學系 === 96 === The clinical importance of drug-eluting stents has been demonstrated by their unparalleled success in preventing restenosis after stenting procedures. However, hypersensitivity reactions caused by their nonerodable polymer coatings and bare-metal stents may result in serious clinical sequelae. In this report, a new biodegradable sirolimus-eluting stent, made from chitosan-based strips fixed by an epoxy compound, was developed. Due to the covalent crosslinks formed in the stent matrix, the fabricated stent had a shape-memory property to memorize its permanent shape. The developed polymeric stent could rapidly expand (~150 s) from its crimped (temporary) state to fully expanded (permanent) state stimulated by hydration, which is advantageous considering avoiding its migration during in vivo deployment. The preliminary animal study showed that this stent had a sufficient mechanical strength and a superior hemocompatibility in the stent-implanted vessel. To enhance the interactions between the poorly soluble anti-proliferative drug (sirolimus) and the hydrophilic stent matrix, a nanoscale drug-entrapment strategy was utilized to construct the sirolimus-eluting stent. Differing from other particle-embedded hydrogel systems, such an entrapment strategy substantially increases the loading efficiency of lipophilic drugs, prevents the drug from aggregation, and beneficially enhances the interaction between the drug and the stent matrix via amphiphilic Pluronic L121 micelles. Our experiments demonstrated that the developed stent can provide a sustained release profile without initial burst effect, thus evading undesirable side effects such as delayed endothelial healing caused by the overdose of sirolimus. When compared to the unloaded stent, neointima formation was significantly suppressed after implantation of the developed sirolimus-eluting stent in rabbit abdominal aortas. These findings suggested that the developed sirolimus-eluting polymeric stent can be a potential alternative for treatment of coronary artery disease.
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