PMID- 25448553
OWN - NLM
STAT- MEDLINE
DCOM- 20160307
LR  - 20150306
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 482
IP  - 1-2
DP  - 2015 Mar 30
TI  - Surface coating mediates the toxicity of polymeric nanoparticles towards 
      human-like macrophages.
PG  - 75-83
LID - S0378-5173(14)00854-0 [pii]
LID - 10.1016/j.ijpharm.2014.11.042 [doi]
AB  - 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.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Grabowski, Nadege
AU  - Grabowski N
AD  - Universite Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clement, 
      92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clement, 92296 
      Chatenay-Malabry Cedex, France.
FAU - Hillaireau, Herve
AU  - Hillaireau H
AD  - Universite Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clement, 
      92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clement, 92296 
      Chatenay-Malabry Cedex, France.
FAU - Vergnaud, Juliette
AU  - Vergnaud J
AD  - Universite Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clement, 
      92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clement, 92296 
      Chatenay-Malabry Cedex, France.
FAU - Tsapis, Nicolas
AU  - Tsapis N
AD  - Universite Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clement, 
      92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clement, 92296 
      Chatenay-Malabry Cedex, France.
FAU - Pallardy, Marc
AU  - Pallardy M
AD  - INSERM UMR 996 Cytokines, Chemokines and Immunopathology, 5 rue JB Clement, 92296 
      Chatenay-Malabry Cedex, France.
FAU - Kerdine-Romer, Saadia
AU  - Kerdine-Romer S
AD  - INSERM UMR 996 Cytokines, Chemokines and Immunopathology, 5 rue JB Clement, 92296 
      Chatenay-Malabry Cedex, France.
FAU - Fattal, Elias
AU  - Fattal E
AD  - Universite Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue JB Clement, 
      92296 Chatenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clement, 92296 
      Chatenay-Malabry Cedex, France. Electronic address: elias.fattal@u-psud.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141118
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Excipients)
RN  - 106392-12-5 (Poloxamer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 9002-89-5 (Polyvinyl Alcohol)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Cell Survival/drug effects
MH  - Chitosan/chemistry/toxicity
MH  - Excipients/chemistry/*toxicity
MH  - Humans
MH  - Lactic Acid/chemistry/*toxicity
MH  - Macrophages/*drug effects
MH  - Nanoparticles/*chemistry/*toxicity
MH  - Poloxamer/chemistry/toxicity
MH  - Polyglycolic Acid/chemistry/*toxicity
MH  - Polyvinyl Alcohol/chemistry/toxicity
OTO - NOTNLM
OT  - Cytotoxicity
OT  - Inflammatory response
OT  - PLGA
OT  - Stabilizer
EDAT- 2014/12/03 06:00
MHDA- 2016/03/08 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/05/22 00:00 [received]
PHST- 2014/11/07 00:00 [revised]
PHST- 2014/11/17 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2016/03/08 06:00 [medline]
AID - S0378-5173(14)00854-0 [pii]
AID - 10.1016/j.ijpharm.2014.11.042 [doi]
PST - ppublish
SO  - Int J Pharm. 2015 Mar 30;482(1-2):75-83. doi: 10.1016/j.ijpharm.2014.11.042. Epub 
      2014 Nov 18.