Differential toxicological response to positively and negatively charged nanoparticles in the rat brain
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Differential toxicological response to positively and negatively charged nanoparticles in the rat brain. / Knudsen, Kristina Bram; Northeved, Helle; Ek, Pramod Kumar; Permin, Anders; Andresen, Thomas Lars; Larsen, Steen; Wegener, Karen Malene; Lam, Henrik Rye; Lykkesfeldt, Jens.
In: Nanotoxicology, Vol. 8, No. 7, 2014, p. 764-774.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Differential toxicological response to positively and negatively charged nanoparticles in the rat brain
AU - Knudsen, Kristina Bram
AU - Northeved, Helle
AU - Ek, Pramod Kumar
AU - Permin, Anders
AU - Andresen, Thomas Lars
AU - Larsen, Steen
AU - Wegener, Karen Malene
AU - Lam, Henrik Rye
AU - Lykkesfeldt, Jens
PY - 2014
Y1 - 2014
N2 - We investigated the potential for systemic and local toxicity after administration of empty nanosized anionic and cationic PEGylated-micelles and non-PEGylated liposomes, without a ligand attached, intended for use in drug-delivery systems. The particles were administered to 5-6-week-old male rats by three intravenous (IV) administrations over a period of one week at a dose of 100 mg/kg bodyweight or after a single intracerebroventricular (ICV) injection at a dose of 50 µg. The particles were stable and well characterised with respect to size and zeta potential. ICV administration of cationic particles was associated with histological changes near the injection site (hippocampus). Here, we detected focal infiltration with phagocytic cells, loss of neurons and apoptotic cell death, which were not observed after administration of the vehicle. No significant difference was found after IV or ICV administration of the anionic micelles with regard to haematology, clinical chemistry parameters or at the pathological examinations, as compared to control animals. Our study suggests that ICV delivery of cationic particles to the brain tissue is associated with toxicity at the injection site.
AB - We investigated the potential for systemic and local toxicity after administration of empty nanosized anionic and cationic PEGylated-micelles and non-PEGylated liposomes, without a ligand attached, intended for use in drug-delivery systems. The particles were administered to 5-6-week-old male rats by three intravenous (IV) administrations over a period of one week at a dose of 100 mg/kg bodyweight or after a single intracerebroventricular (ICV) injection at a dose of 50 µg. The particles were stable and well characterised with respect to size and zeta potential. ICV administration of cationic particles was associated with histological changes near the injection site (hippocampus). Here, we detected focal infiltration with phagocytic cells, loss of neurons and apoptotic cell death, which were not observed after administration of the vehicle. No significant difference was found after IV or ICV administration of the anionic micelles with regard to haematology, clinical chemistry parameters or at the pathological examinations, as compared to control animals. Our study suggests that ICV delivery of cationic particles to the brain tissue is associated with toxicity at the injection site.
KW - Faculty of Health and Medical Sciences
KW - micelles
KW - liposomes
KW - hippocampus
KW - Apoptosis Regulatory Proteins
U2 - 10.3109/17435390.2013.829589
DO - 10.3109/17435390.2013.829589
M3 - Journal article
C2 - 23889261
VL - 8
SP - 764
EP - 774
JO - Nanotoxicology
JF - Nanotoxicology
SN - 1743-5390
IS - 7
ER -
ID: 99766345