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Stent coating by electrospinning with chitosan/poly-cyclodextrin based nanofibers loaded with simvastatin for restenosis prevention
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2020-03-13 , DOI: 10.1016/j.ejpb.2019.12.017
Dyhia Kersani , Justine Mougin , Marco Lopez , Stéphanie Degoutin , Nicolas Tabary , Frédéric Cazaux , Ludovic Janus , Mickaël Maton , Feng Chai , Jonathan Sobocinski , Nicolas Blanchemain , Bernard Martel

The main cause of failure of angioplasty stenting is restenosis due to neointimal hyperplasia, a too high proliferation of smooth muscle cells (SMC). The local and sustained delivery of selective pleiotropic drugs to limit SMC proliferation seems to be the hopeful solution to minimize this post surgery complication. The aim of this study is to develop a stent covered by nanofibers (NFs) produced by electrospinning, loaded with simvastatin (SV), a drug commonly used for restenosis prevention. NFs were prepared from the electrospinning of a solution containing SV and a mixture of chitosan (cationic) and β-cyclodextrin (CD) polymer (anionic) which form together a polyelectrolyte complex that makes up the NFs matrix. First, the SV/CD interactions were studied by phase solubility diagram, DRX and DSC. The electrospinning process was then optimized to cover a self-expandable NiTiNOL stent and the mechanical resistance of the NFs sheath upon its introduction inside the delivery catheter was considered, using a crimper apparatus. The morphology, coating thicknesses and diameters of nanofibers were studied by scanning electron microscopy. The SV loading rates on the stents were controlled by the electrospinning time, and the presence of SV in the NFs was confirmed by FTIR. NFs stability in PBS pH 7.4 buffer could be improved after thermal post-treatment of NFs and in vitro release of SV in dynamic conditions demonstrated that the release profiles were influenced by the presence of CD polymer in NFs and by the thickness of the NFs sheath. Finally, a covered stent delivering 3 µg/mm2 of SV within 6 hours was obtained, whose efficiency will be investigated in a further in vivo study.



中文翻译:

通过使用负载有辛伐他汀的壳聚糖/聚环糊精基纳米纤维静电纺丝制成的支架涂层,以预防再狭窄

血管成形术支架置入失败的主要原因是由于新内膜增生引起的再狭窄,平滑肌细胞(SMC)增殖过高。选择性和多效性药物的局部和持续给药以限制SMC的增殖似乎是减少这种术后并发症的有希望的解决方案。这项研究的目的是开发一种通过静电纺丝生产的纳米纤维(NFs)覆盖的支架,该支架上装有辛伐他汀(SV)(一种通常用于预防再狭窄的药物)。从包含SV的溶液和壳聚糖(阳离子)和β-环糊精(CD)聚合物(阴离子)的混合物的电纺丝制备NF,它们共同形成构成NFs基质的聚电解质复合物。首先,通过相溶解度图,DRX和DSC研究了SV / CD相互作用。压接装置。通过扫描电子显微镜研究了纳米纤维的形貌,涂层厚度和直径。支架上的SV加载速率由电纺丝时间控制,并且FTIR证实了NFs中存在SV。在对NFs进行热后处理和在动态条件下体外释放SV后,可以改善PBS pH 7.4缓冲液中NFs的稳定性,这表明释放曲线受到NFs中CD聚合物的存在和NFs鞘厚度的影响。 。最后,获得了在6小时内可递送3 µg / mm 2 SV的覆盖支架,其效率将在进一步的体内研究中进行研究。

更新日期:2020-03-16
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