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Stent coating by electrospinning with chitosan/poly-cyclodextrin based nanofibers loaded with simvastatin for restenosis prevention

Abstract : 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 h was obtained, whose efficiency will be investigated in a further in vivo study.
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https://hal.univ-lille.fr/hal-02927091
Contributeur : Lilloa Université de Lille <>
Soumis le : mardi 1 septembre 2020 - 13:38:04
Dernière modification le : mercredi 4 novembre 2020 - 09:48:07

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Dyhia Kersani, Justine Mougin, Marco Lopez, Stephanie Willai, Nicolas Tabary, et al.. Stent coating by electrospinning with chitosan/poly-cyclodextrin based nanofibers loaded with simvastatin for restenosis prevention. European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2020, European Journal of Pharmaceutics and Biopharmaceutics, 150, pp.156-167. ⟨10.1016/j.ejpb.2019.12.017⟩. ⟨hal-02927091⟩

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