Study On Intervention Effect Of Liver Targeted Micelle Encapsulate Resveratrol In The Nonalcoholic Fatty Liver

Resveratrol(Res)has anti-inflammatory,anti-oxidation and anti-tumor effects.It is a kind of plant polyphenols,which has poor stability and is very insoluble in water.Nonalcoholic fatty liver disease(NAFLD)is a pathological syndrome of hepatic fat accumulation and degeneration in the absence of drinking history,which seriously damages human health,and the number of NAFLD patients is still increasing every year.Currently,poor drug specificity with great side effects is a major obstacle for the treatment of NAFLD.In order to solve the problem,this paper designed a liver-targeting peptide nanosphere-loaded Res drug delivery system.The in vitro and in vivo experiments showed that the constructed vector can effectively deliver Res to the hepatic cells,realize liver-targeted goals,and improve the bioavailability of Res.The research contents mainly include three aspects:1.Amphipathic peptides were obtained through lysozyme enzymatic hydrolysis,which were self-assembled into polypeptide nanospheres with uniform particle size.They were then used to embed hydrophobic nanoparticles drug Res with their peptide hydrophobic core;galactose and oxidized starch were covalent cross-linked,and self-assembled with polypeptide nanospheres to form polypeptide nanospheres in aqueous solution.The physical and chemical properties of the nanospheres were investigated according to the TEM images,particle size,Zeta potential and stability.The results showed that the nanospheres were spherical and the particle size was uniform,about 89 nm.The drug loading of Res was 14.5%.The Zeta potential of liver-targeting molecule of peptide nanospheres changed from positive to negative.2.Vector bio-safety and liver-targeting effects were validated at cellular and animal levels,respectively.At the cellular level,firstly,the nanospheres were screened out by CCK-8 for safe administration at a concentration of 100 ?g / mL;further,the effect of liver-targeting on the carrier was detected by flow cytometry.The results showed that when compared with the single nanospheres alone,more galactose-loaded nanospheres were ingested by HepG2 cells,indicating that galactose had a certain degree of liver-targeting effect.The results of biochemical analysis and pathology showed that no apparent toxicity was detected at the level of animals after 7 days of intravenous injection of nanospheres;then detected by the multi-function imager the drug went into the body and accumulated in the liver.3.For NAFLD,at cellular level,mimic hepatic lipid deposition with palmitate was performed in vitro.The effect of embedding Res on lipid deposition was better than that of free Res.The results of protein and gene level showed that Res could improve non-alcoholic fatty liver by increasing SIRT1 deacetylation activity,and inhibiting the expression of SREBP1 c.In summary,the galactose-modified polypeptide nanospheres has the characteristics of liver-targeting.This article laid theoretical foundation for the study of non-alcoholic fatty liver-targeting drug research and development.