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Small: nano delivery system can reduce the hepatotoxicity of small molecule drugs

wallpapers News 2020-09-09

nano delivery system has great potential for the treatment of diseases such as cancer infection. However an important problem in the clinical transformation of nanodrugs is toxicity especially hepatotoxicity. Because a large number of preclinical studies have shown that the accumulation of nanodrugs in the liver is significantly higher than that of small molecule prototypes. However for many nanodrugs that have been approved for clinical use there is no data to show that their hepatotoxicity has increased. Based on the above facts little is known about the hepatotoxicity caused by nano delivery system its important influencing factors (except the hepatotoxicity of nanoparticles themselves). The lack of research in this field leads to the avoidance of small molecule drugs with hepatotoxicity in the development of nanodrugs for clinical transformation. Therefore it is urgent to study the hepatotoxicity of nanodrugs the main influencing factors. The preliminary study of

Andrew Wang research group found that the hepatotoxicity of small molecule drug wortmannin (wtmn) prepared into nanoparticles was reduced in mice. Based on the findings Professor Andrew Wang Dr Yu MI their collaborator Feifei of Institute of medicinal plants Chinese Academy of Medical Sciences Associate researcher Yang selected three kinds of small molecule drugs with hepatotoxicity such as chlorpromazine (CPZ) 7-ethyl-10 Hydroxycamptothecin (SN-38) wtmn to prepare nanoparticles. The hepatotoxicity induced by nanoparticles was evaluated the main influencing factors were studied in detail.

were used to prepare nanoparticles of the above three hepatotoxic compounds. After intravenous administration of 1 / 2 MTD in mice the serum alanine aminotransferase (ALT) aspartate aminotransferase (AST) were used as indicators to evaluate their hepatotoxicity. The results showed that the levels of ALT AST in the nanoparticles group were significantly lower than those in the small molecule drug group. The results of heme oxygenase-1 (HO-1) manganese superoxide dismutase (Mn SOD) staining by immunohistochemistry further confirmed that the liver injury in the small molecule drug group was more serious than that in the nanoparticles group. The results were verified in different strains of mice after single / multiple administration. Nanoparticles of a certain size will be absorbed by macrophages after entering the liver. The researchers further elucidated the effect of macrophage uptake on hepatotoxicity. The results showed that the uptake of nanoparticles by macrophages in vitro could significantly improve the survival rate of hepatocytes the hepatotoxicity of nanoparticles group was significantly increased after the macrophages were knocked out in vivo. It is worth noting that: different from normal mice the values of AST ALT in the nanoparticles group were higher than those in the small molecule drug group after macrophage knockout the increased value of positive area in the immunohistochemistry was also significantly higher than that before after macrophage knockout. Therefore the researchers concluded that the uptake of macrophages is an important factor in the low hepatotoxicity of nanodrugs.

the results showed that nano delivery system can reduce the hepatotoxicity caused by hepatotoxic small molecule compounds the uptake of nanoparticles by macrophages is the key factor to reduce the hepatotoxicity. It is exciting that this research provides a new clinical application of nano delivery system which is to prepare hepatotoxic compounds into nano preparations for clinical transformation. Based on the fact that many compounds have no choice but to give up due to hepatotoxicity in the process of research development even the drugs approved for marketing are forced to be taken off the shelf due to hepatotoxicity this study provides a new strategy to overcome the hepatotoxicity problem which is a bridge between drug delivery system clinical medicine.

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