title: Differential toxicological response to positively and negatively charged nanoparticles in the rat brain.
abstract: 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.
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Kristina Bram
authors.initials: KB
authors.lastname: Knudsen
authors.forename: Helle
authors.initials: H
authors.lastname: Northeved
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Ek
authors.forename: Anders
authors.initials: A
authors.lastname: Permin
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andresen
authors.forename: Steen
authors.initials: S
authors.lastname: Larsen
authors.forename: Karen Malene
authors.initials: KM
authors.lastname: Wegener
authors.forename: Henrik Rye
authors.initials: HR
authors.lastname: Lam
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008297:Male; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008081:Liposomes; D008823:Micelles; D011092:Polyethylene Glycols; D053148:Caspase 3