In vivo toxicity of cationic micelles and liposomes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Kristina Bram Knudsen, Helle Northeved, Pramod Kumar Ek, Anders Permin, Torben Gjetting, Thomas L Andresen, Steen Larsen, Karen Malene Wegener, Jens Lykkesfeldt, Kim Jantzen, Steffen Loft, Peter Møller, Martin Roursgaard

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 100mg/kg and sacrificed after 24 or 48h, or 24h after the last of three intravenous injections of 100mg/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.

OriginalsprogEngelsk
TidsskriftNanomedicine: Nanotechnology, Biology and Medicine
Vol/bind11
Udgave nummer2
Sider (fra-til)467-477
Antal sider11
ISSN1549-9634
DOI
StatusUdgivet - 25 feb. 2015

ID: 124426961