Safety and toxicology of the intravenous administration of Ang2-siRNA plasmid chitosan magnetic nanoparticles

Abstract

This aim of the present study was to investigate the safety and toxicology of intravenous administration of angiopoietin-2 (Ang2)-small interfering (si)RNA plasmid-chitosan magnetic nanoparticles (CMNPs). Ang2-CMNPs were constructed and subsequently administered at different doses to mice and rats via the tail vein. The acute (in mice) and chronic toxicity (in rats) were observed. The results of the acute toxicity assay revealed that the LD50 mice was >707.0 mgkg-1d-1, and the general condition of mice revealed no obvious abnormalities. With the exception of the high dose group (254.6 mgkg-1d-1), which exhibited partial lung congestion, the other groups exhibited no obvious abnormalities. Results of the chronic toxicity assay demonstrated that the non-toxic dose of Ang2-CMNPs in the rat was >35.35 mgkg-1d-1 for 14 days. The rat general condition and blood biochemistry indexes revealed no obvious abnormality. The blood routine indexes and lung/body ratio of each treatment group were higher when compared with the control group. The middle-and high-dose groups exhibited chronic pulmonary congestion, whilst the low-dose and control groups exhibited no abnormality. Similarly, the other organs revealed no obvious abnormality. Ang2-CMNPs have good safety at a certain dose range and may be considered as the target drug carrier.