Journal article
In vivo toxicity of cationic micelles and liposomes
University of Copenhagen1
H. Lundbeck A/S2
Department of Micro- and Nanotechnology, Technical University of Denmark3
Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark4
Center for Nanomedicine and Theranostics, Centers, Technical University of Denmark5
National Food Institute, Technical University of Denmark6
This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the last of three intravenous injections of 100 mg/kg every other day.
Histological evaluation of liver, lung and spleen, clinical chemistry parameters, and hematology indicated little effect of treatment. DNA strand breaks were increased in the lung and spleen. Further, in the dose response study we found unaltered expression levels of genes in the antioxidant response (HMOX1) and repair of oxidized nucleobases (OGG1), whereas expression levels of cytokines (IL6, CXCL2 and CCL2) were elevated in lung, spleen or liver.
The results indicate that assessment of genotoxicity and gene expression add information on toxicity of nanocarriers, which is not obtained by histology and hematology.
Language: | English |
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Year: | 2015 |
Pages: | 467-477 |
ISSN: | 15499642 and 15499634 |
Types: | Journal article |
DOI: | 10.1016/j.nano.2014.08.004 |
ORCIDs: | 0000-0002-6514-8407 , 0000-0001-9552-8518 , 0000-0002-2021-1249 , 0000-0002-7206-0032 and Andresen, Thomas Lars |
Animals Cations Ccl2 protein, rat Chemokine CCL2 Chemokine CXCL2 Cxcl2 protein, rat DNA Damage DNA Glycosylases Drug Delivery Systems Faculty of Health and Medical Sciences Gene Expression Regulation Gene Transfer Techniques Heme Oxygenase (Decyclizing) Hmox1 protein, rat Liver Lung Male OGG1 protein, rat Rats Spleen