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Drug delivery based on nanostructured microparticles and hydrogels for intra-articular treatment of osteoarthritis

Defense Thèse de doctorat : Univ. Genève, 2017 - Sc. 5161 - 2017/12/19
Abstract Osteoarthritis (OA) is the most common type of arthritis affecting 80 % of the world's population over 75 years. Despite this rising trend, there is as yet no cure for OA. This thesis aimed to design two efficient biodegradable and biocompatible extended release formulations for intra-articular (IA) administration to treat the disease and improve the quality of life of patients. Firstly, Nanocrystal-Polymer Particles (NPPs), with a very high drug loading of PH-797804 or Kartogenin, were formulated by a wet-milling/spray drying process. Secondly, a thermosensitive hyaluronic acid able to form nanoparticles in situ was designed and developed as a new way of lubricating joints. In vivo, both of these technologies showed a positive effect based on histological scoring, epiphyseal thickness, OA biomarkers and prolonged IA persistence in a murine OA model. This thesis provides proofs-of-concept of novel and innovative extended drug delivery system/viscosupplement with the potential to treat human OA.
Keywords OsteoarthritisDrug-deliveryIntra-articularDisease-modifying osteoarthritis drugCarriersPolymersBiodegradable microparticlesNanocrystalsPH-797804P38α/β MAPK inhibitorKartogeninCBFβ-RUNX1 pathway activatorInflammatory and mechanistic mouse modelsNanocrystal-Polymer ParticlesHA NanoHyaluronic acidHydrogelsThermosensitive
URN: urn:nbn:ch:unige-1042581
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Research group Technologie pharmaceutique
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MAUDENS, Pierre Marc Xavier. Drug delivery based on nanostructured microparticles and hydrogels for intra-articular treatment of osteoarthritis. Université de Genève. Thèse, 2017. https://archive-ouverte.unige.ch/unige:104258

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Deposited on : 2018-05-09

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