title: Surface coating mediates the toxicity of polymeric nanoparticles towards human-like macrophages.
abstract: The purpose of this study was to investigate the toxicity of a series of poly(lactide-co-glycolic) (PLGA) nanoparticles on human-like THP-1 macrophages. Positively-, negatively-charged and neutral nanoparticles (200 nm) were prepared using chitosan (CS), poloxamer 188 (PF68) and poly(vinyl alcohol) (PVA) as stabilizer. Stabilizer-free PLGA nanoparticles were obtained as well. When used at therapeutically relevant concentrations (up to 0.1 mg/mL in vitro), all tested nanoparticles showed no or scarce signs of toxicity, as assessed by cell mitochondrial activity, induction of apoptosis and necrosis, production of intracellular reactive oxygen species (ROS) and secretion of pro-inflammatory cytokines. At high concentrations (above 1mg/mL), cytotoxicity was found to be induced by the presence of stabilizers, whatever the toxicological pattern of the stabilizer itself. While stabilizer-free PLGA nanoparticles exerted no cytotoxicity, the slightly cytotoxic CS polymer conferred PLGA nanoparticles significant cytotoxicity when used as nanoparticle stabilizer; more surprisingly, the otherwise innocuous PVA and PF68 polymers also conferred a significant cytotoxicity to PLGA nanoparticles. These results unveiled the critical toxicological contribution played by stabilizers used for the formulation of PLGA nanoparticles when used at high concentrations, which may have implications for local toxicities of PLGA-based nanomedicine, and provided additional insight in cytotoxic effects of internalized nanoparticles.
authors.affiliation: Université Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Grabowski
authors.affiliation: Université Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Hillaireau
authors.affiliation: Université Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Vergnaud
authors.affiliation: Université Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
authors.affiliation: INSERM UMR 996 Cytokines, Chemokines and Immunopathology, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: INSERM UMR 996 Cytokines, Chemokines and Immunopathology, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France.
authors.forename: Saadia
authors.initials: S
authors.lastname: Kerdine-Römer
authors.affiliation: Université Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clément, 92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France. Electronic address: elias.fattal@u-psud.fr.
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000633:toxicity; D005079:Excipients / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D020442:Poloxamer / Q000737:chemistry / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry / Q000633:toxicity*; D011142:Polyvinyl Alcohol / Q000737:chemistry / Q000633:toxicity
chemical_list: D005079:Excipients; D020442:Poloxamer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol; D048271:Chitosan
keywords: Cytotoxicity; Inflammatory response; PLGA; Stabilizer