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 mg·kg-1·d-1, and the general condition of mice revealed no obvious abnormalities. With the exception of the high dose group (254.6 mg·kg-1·d-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 mg·kg-1·d-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.

Biological Safety and Biodistribution of Chitosan Nanoparticles

“…Clinical examination of animals did not reveal any behavioral signs of distress or pain following CNP administration. The available published data indicate that both single and multiple intravenous administrations of CNPs and their derivatives at doses similar to ours are tolerated satisfactorily by animals without inducing a change in body weight [25,30,48,59,60]. The absence of differences in the clinical and biochemical blood tests between the groups suggests that the cause of weight loss was not a "classic" cytotoxic effect.…”

Co‐delivery of hypoxia inducible factor‐1α small interfering RNA and 5‐fluorouracil to overcome drug resistance in gastric cancer SGC‐7901 cells

“…At the beginning of the study, we selected CS nanoparticles as a delivery vector for 5-FU and siRNA, which has been widely used as gene carrier. 35,36 Following this, an evaluation of the properties of the nanoparticles was conducted, including entrapment efficiency, particle size and zeta potential. The binding efficiency of CS nanoparticles and siRNA was evaluated by agarose gel electrophoresis and the results obtained showed that CS nanoparticles can effectively bind siRNA.…”

“…At the beginning of the study, we selected CS nanoparticles as a delivery vector for 5-FU and siRNA, which has been widely used as gene carrier 35,36. (A) The accumulation of Rho-123 in cells.…”

Synthesis of Imatinib‐loaded chitosan‐modified magnetic nanoparticles as an anti‐cancer agent for pH responsive targeted drug delivery

“…Moreover, CS has been reported as a successful nanocarrier of antitumoral drugs . Also, CS coated MNPs have been declared to increase the effect of magnetic hyperthermia in glioblastoma treatment and reducing toxicity in drug delivery to biological systems and gene therapy . Furthermore, since CS has primary amino groups, it can be utilized for controlled drug release, mucoadhesion, in situ gellation, transfection, permeation enhancement, and efflux pump inhibition .…”