Differential toxicological response to positively and negatively charged nanoparticles in the rat brain

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 - 2014/11

Y1 - 2014/11

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

SN - 1743-5390

VL - 8

SP - 764

EP - 774

JO - Nanotoxicology

JF - Nanotoxicology

IS - 7

ER -