In vivo toxicity of cationic micelles and liposomes

AbstractThis 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.From the Clinical EditorThis 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

Legacy data sharing to improve drug safety assessment: The eTOX project

The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility