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Sustained release systems for the perivascular administration of atorvastatin to prevent vein graft failure

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Defense Thèse de doctorat : Univ. Genève, 2017 - Sc. 5057 - 2017/02/28
Abstract The aim of the present thesis work was to explore sustained and local statin delivery approaches for the prevention of vein graft failure. These systems are meant to be applied perivascularly (around the vessel) during the open surgical intervention. We developed an atorvastatin delivery system containing cross-linked hyaluronic acid hydrogel and poly(lactic-co-glycolic) acid microparticles. This system allowed for a fast (over three days) and sustained (over four weeks) release of atorvastatin. The formulation was applied in vivo on the carotid artery of a rodent model of vein graft failure. Intimal hyperplasia development was inhibited by 61 % compared to control. On a porcine model of vein graft failure, a dose of 10 mg of atorvastatin applied perivascularly was not sufficient to inhibit intimal hyperplasia. In a parallel project we combined the fast and sustained release potential with mechanical support, a polyethylene terephthalate mesh coated with a layer of poly(lactic-co-glycolic) acid containing ATV was developed.
Keywords Intimal hyperplasiaVein graft failureAtorvastatinPLGAMicroparticlesMeshHydrogelPerivascular
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URN: urn:nbn:ch:unige-929625
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Thesis (11.8 MB) - public document Free access
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Research group Technologie pharmaceutique
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MYLONAKI, Ioanna. Sustained release systems for the perivascular administration of atorvastatin to prevent vein graft failure. Université de Genève. Thèse, 2017. doi: 10.13097/archive-ouverte/unige:92962 https://archive-ouverte.unige.ch/unige:92962

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Deposited on : 2017-03-31

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