Abstract
A new nanoscale drug carrier could have a variety of therapeutic and diagnostic uses provided that the carrier is biocompatible in vivo. Carbon nano-onions (CNOs), is one such potential carbon-based drug carrier. Previous work in our laboratory showed that single and repeated administration of CNOs (125, 250 or 500 μg) was well-tolerated by female BALB/c mice. Hence, this study aimed to investigate the extent of CNO accumulation in various organs as well as its effect on drug metabolism and oxidative stress. Organs that had been frozen at necropsy were sliced and examined for the appearance of CNO aggregates. Liver microsomes that had been prepared previously were used for the analysis of total CYP450 and CYP3A catalytic activity as determined by erythromycin N-demethylation. Organ homogenates that had also been previously prepared were used to determine lipid peroxidation via the malondialdehyde assay. Histological examination of organ slices revealed a dose-dependent accumulation of CNO aggregates in the spleen, liver and lungs, with a trace amount of aggregates appearing in the kidney. Three doses of CNOs resulted in ~2.6 times higher accumulation of CNO aggregates compared to the single dose. Furthermore, CNO aggregates in the liver did not impact CYP450 enzymes, as total hepatic CYP450 as well as CYP3A catalytic activity and protein levels showed no significant changes between the treatment groups compared to vehicle control. Lastly, CNOs did not induce lipid peroxidation, as indicated by the unchanged malondialdehyde levels of liver microsomes and organ homogenates. This study provides the first evidence that intravenous administration of oxi-CNOs was non-toxic to BALB/c mice, indicating a potential novel, safe drug carrier.