In vivo toxicity of cationic micelles and liposomes

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

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Abstract

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.
Original languageEnglish
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume11
Issue number2
Pages (from-to)467-477
Number of pages11
ISSN1549-9634
DOIs
Publication statusPublished - 2015

Bibliographical note

This is an open access article under the CC BY-NC-SA license

Keywords

  • Nanocarriers
  • Liposomes
  • Micelles
  • In vivo toxicology
  • Nanomedicine

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