title: In vivo toxicity of cationic micelles and liposomes.
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.
  
  
  BACKGROUND
  This study investigates the toxicity of cationic micelles and liposomes utilized as nanocarriers in gene and drug delivery, demonstrating its effects on the lungs, spleen and liver.
authors.affiliation: H. Lundbeck A/S, Valby, Denmark; Faculty of Health and Medical Science, University of Copenhagen, Denmark.
authors.forename: Kristina Bram
authors.initials: KB
authors.lastname: Knudsen
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Northeved
authors.affiliation: Center for Nanomedicine and Theranostics, Technical University of Denmark, DTU Nanotech, Lyngby, Denmark.
authors.forename: Pramod E K
authors.initials: PE
authors.lastname: Kumar
authors.affiliation: DTU Food, Technical University of Denmark, Søborg, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Permin
authors.affiliation: Center for Nanomedicine and Theranostics, Technical University of Denmark, DTU Nanotech, Lyngby, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Gjetting
authors.affiliation: Center for Nanomedicine and Theranostics, Technical University of Denmark, DTU Nanotech, Lyngby, Denmark.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andresen
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Larsen
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Karen Malene
authors.initials: KM
authors.lastname: Wegener
authors.affiliation: Faculty of Health and Medical Science, University of Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Faculty of Health and Medical Science, University of Copenhagen, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Jantzen
authors.affiliation: Faculty of Health and Medical Science, University of Copenhagen, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.affiliation: Faculty of Health and Medical Science, University of Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.affiliation: Faculty of Health and Medical Science, University of Copenhagen, Denmark. Electronic address: mwro@sund.ku.dk.
authors.forename: Martin
authors.initials: M
authors.lastname: Roursgaard
mesh_terms: D000818:Animals; D002412:Cations / Q000009:adverse effects* / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000096:biosynthesis; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000187:drug effects; D018014:Gene Transfer Techniques; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D008081:Liposomes / Q000009:adverse effects* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D008823:Micelles; D051381:Rats; D013154:Spleen / Q000187:drug effects
chemical_list: D002412:Cations; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D008081:Liposomes; D008823:Micelles; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D045647:DNA Glycosylases; C483741:OGG1 protein, rat
keywords: In vivo toxicology; Liposomes; Micelles; Nanocarriers; Nanomedicine