The Safety Assessment And Pharmacokinetics Study Of Nanoparticles Of Fe₂O₃ Coated With Glutamic Acid

Nanometer is a kind of scale unit. One nanometer is 10-9 meter. Nanoparticles are crystals or noncrystals which are less than 100 nanometers. Having some novel features, which are not possessed by corresponding routine materials, they promote more medical advances. In recent years, some medicine coring Fe2O3 for magnetic hyperthermia on tumor have made it become a promising useful therapeutic method. But are these medicine safe? What is the process of pharmacokinetics? Conclusive data about them are notably lacking. To explore the safety and pharmacokinetics of nanoparticles of Fe2O3 coated with Glutamic acid(abbreviation: nano-Fe2O3-Glu), whose diameter is 15 nanometers, a series of tests have been conducted, including acute, sub-acute toxicity tests, mutagenicity tests and pharmacokinetics tests. The results are as follows.①In this experiment system the half lethel dose of nano-Fe2O3-Glu after i.v. in mice is 247.66mg/(kg?bw), and after i.p. continuously in rats for 14 days, nano-Fe2O3-Glu have not led to pathological changes although increasing the quantity of leucocyte cells and the ratio of neutrophilic granulocyte.②Compared with the control group, Ames test, micronucleus test and sperm deformity test in mice show that nano-Fe2O3-Glu can not induce reversion of TA97, TA98, TA100 and TA102 bacterial testing system with or without S9mix, the mutation of bone marrow cells and deformity of sperms in mice.③When 59Fe is used as a tracer to investigate the pharmacokinetics of nano-Fe2O3-Glu, after i.v. in mice by 5.12 mg/(kg?bw), nano-Fe2O3-Glu is found to be distributed widely in various organs, and the concentration of liver and spleen is higher than that of other organs. Moreover, the time of peak concentration of every organ is not unanimous. In addition, nano-Fe2O3-Glu can be surveyed to permeate the barriers of brain, eyes and genitals. The time-concentration curve of nano-Fe2O3-Glu is fit mainly to a two-compartment model[c=29.09e-4.29t+1.13e-0.009673t]. Its T1/2(α)equals about to 0.16 hour and T1/2(β)71.65 hours. In a word, we can draw a conclusion that nano-Fe2O3-Glu do not indicate notable toxicity and mutagenicity. Nano-Fe2O3-Glu are distributed widely in various organs especially in liver and spleen, for which liver and spleen can be thought as target organs of nano-Fe2O3-Glu. Besides, the concentration of nano-Fe2O3-Glu in blood is linked to that in liver and spleen. It should be attached importance to the potential toxicity because nano-Fe2O3-Glu can be observed to permeate the barriers of brain, eyes and genitals.