TY - JOUR
T1 - In vivo toxicity of cationic micelles and liposomes
AU - Knudsen, Kristina Bram
AU - Northeved, Helle
AU - Kumar Ek, Pramod
AU - Permin, Anders
AU - Gjetting, Torben
AU - Andresen, Thomas L
AU - Larsen, Steen
AU - Wegener, Karen Malene
AU - Lykkesfeldt, Jens
AU - Jantzen, Kim
AU - Loft, Steffen
AU - Møller, Peter
AU - Roursgaard, Martin
N1 - Copyright © 2014. Published by Elsevier Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - Faculty of Health and Medical Sciences
KW - Nanocarriers
KW - Liposomes
KW - Micelles
KW - In vivo toxicology
KW - Nanomedicine
U2 - 10.1016/j.nano.2014.08.004
DO - 10.1016/j.nano.2014.08.004
M3 - Journal article
C2 - 25168934
SN - 1549-9634
VL - 11
SP - 467
EP - 477
JO - Nanomedicine: Nanotechnology, Biology and Medicine
JF - Nanomedicine: Nanotechnology, Biology and Medicine
IS - 2
ER -