Mathieu Riffault1, Jean-Luc Six2, Patrick Netter1, Pierre Gillet3, Laurent Grossin1. 1. Ingénierie Moléculaire et Physiopathologie Articulaire, Unité Mixte de Recherche 7365, Centre National de la Recherche Scientifique - Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye CS 50184, 54505, Vandœuvre Lès Nancy cedex, France. 2. Laboratoire de Chimie-Physique Macromoléculaire, Unité Mixte de Recherche 7568, Centre National de la Recherche Scientifique - Institut National Polytechnique de Lorraine, ENSIC, Nancy, France. 3. Ingénierie Moléculaire et Physiopathologie Articulaire, Unité Mixte de Recherche 7365, Centre National de la Recherche Scientifique - Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye CS 50184, 54505, Vandœuvre Lès Nancy cedex, France. pierre.gillet@univ-lorraine.fr.
Abstract
PURPOSE: Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. METHODS: Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. RESULTS: Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. CONCLUSIONS: Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint.
PURPOSE: Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. METHODS: Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. RESULTS: Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. CONCLUSIONS: Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint.
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Authors: Simón Méndez-Ferrer; Tatyana V Michurina; Francesca Ferraro; Amin R Mazloom; Ben D Macarthur; Sergio A Lira; David T Scadden; Avi Ma'ayan; Grigori N Enikolopov; Paul S Frenette Journal: Nature Date: 2010-08-12 Impact factor: 49.962
Authors: Hervé Zille; Joseph Paquet; Christel Henrionnet; Julien Scala-Bertola; Michèle Leonard; Jean Luc Six; Frantz Deschamp; Patrick Netter; José Vergès; Pierre Gillet; Laurent Grossin Journal: Biomed Mater Eng Date: 2010 Impact factor: 1.300
Authors: Steven Lotz; Susan Goderie; Nicolas Tokas; Sarah E Hirsch; Faizzan Ahmad; Barbara Corneo; Sheila Le; Akhilesh Banerjee; Ravi S Kane; Jeffrey H Stern; Sally Temple; Christopher A Fasano Journal: PLoS One Date: 2013-02-20 Impact factor: 3.240