title: PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Riffault
authors.affiliation: Laboratoire de Chimie-Physique Macromoléculaire, Unité Mixte de Recherche 7568, Centre National de la Recherche Scientifique - Institut National Polytechnique de Lorraine, ENSIC, Nancy, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Six
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Netter
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gillet
authors.affiliation: 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.
authors.forename: Laurent
authors.initials: L
authors.lastname: Grossin
mesh_terms: D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020219:Chondrogenesis; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000648:ultrastructure; D019344:Lactic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy / Q000473:pathology; D010012:Osteogenesis; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA; hyaluronate; nanoparticles; osteoarticular; vectorization