Nanosphères polymères à couverture de hyaluronate pour la délivrance ciblée de molécules actives dans le traitement des affections du cartilage

Abstract : The aim of the present work was to develop a nanoparticular system of vectorisation of therapeutic interests molecules for the treatment of osteoarticular pathologies. Nowadays, treatments aim more at treating the symptoms that to stop the pathology progress, major difficulty being the release of molecules and their addressing. The objectives of such a research consist on two working axes, (1) the development of nanoparticulaires systems, in which we have encapsulated various molecules (fluorescent tracer, pharmacological compounds) and (2) the evaluation of systems so obtained on different cells contingents. The originality of our work is on one hand the process of preparation of nanoparticles and on the other hand the coating of nanoparticles with HA in order to increase interactions with articular cells, chondrocytes. Thanks to our technique of synthesis, we could prepare different types of nanoparticles, loading several molecules like dextran FITC (biological tracer) or active principles, as the chondroïtin sulphate or hyaluronic acid (HA). The choice of the HA for coated the nanoparticules surface was decided because it is well known that chondrocytes express in their surface a specific receptor of hyaluronique acid, CD44. Once the process of synthesis and the coating of nanoparticles established, our job consisted in showing the harmlessness of particles in vitro (cytocompatibility, lack of pathogenic effects, preservation of the matrix biosynthesis/turnover) and the interest of coating nanoparticules by HA to facilitate the internalisation by chondrocytes. We showed a stronger affinity of nanoparticles covered with HA (versus PVA-coated nanoparticles) for chondrocytes (versus synoviocytes). We also tested our cells targetting system by injecting nanoparticles by intraarticular way at healthy animals. The obtained results confirmed those observed during the in vitro experiments what allows us of validated the concept of vectorization of therapeutic molecules by means of nanoparticular systems for the osteoarticular diseases.
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Hamed Laroui. Nanosphères polymères à couverture de hyaluronate pour la délivrance ciblée de molécules actives dans le traitement des affections du cartilage. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2007. Français. ⟨NNT : 2007NAN10151⟩. ⟨tel-01748397⟩

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