Knudsen, K.B.5; Northeved, H.6; Ek, Pramod Kumar7; Permin, Anders8; Andresen, Thomas Lars1; Larsen, S.6; Wegener, K. M.6; Lam, Henrik Rye4; Lykkesfeldt, Jens9
1 Department of Micro- and Nanotechnology, Technical University of Denmark2 Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark3 Center for Nanomedicine and Theranostics, Center, Technical University of Denmark4 National Food Institute, Technical University of Denmark5 University of Copenhagen6 H. Lundbeck A/S7 Risø National Laboratory for Sustainable Energy, Technical University of Denmark8 Office for Innovation & Sector Services, Administration, Technical University of Denmark9 DHI Denmark
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.
Nanotoxicology, 2014, Vol 8, Issue 7, p. 764-774
The Faculty of Health Science; micelles; liposomes; hippocampus; Apoptosis Regulatory Proteins; Micelles; Liposomes; Hippocampus; Apoptosis