The Prophylactic Of Magnetic Poly D, L-Lactide-co-Glycolide Oxymatrine Nanoparticles On Liver Fibrosis

BackgroundHepatitis B is one of the most common infectious diseases in China.And 25%-443%of these patients will develop to hepatic cirrhosis even liver cancer.Liver fibrosis is a prepathologic state of cirrhosis,which plays a pivotal role in the carcinogenesis of hepatocellular carcinoma(HCC).The current investigation showed that liver fibrosis,and even cirrhosis at early stage,may be reversible.Most of patients with hepatitis B and hepatitis C have hepatic fibrosis in different degree.Therefore,the prevention of liver fibrosis is very important both in theory and in practice.Oxymatrine(OM) is one of the quinolizidine alkaloids extracted from traditional Chinese herbal medicine Sophora japonica(sophora flavescesn Ait),Sophora subprostrata and Sophora alopecuroides.It has been reported that OM plays important roles in inhibiting hepatitis B,protecting hepatocytes and antihepatic fibrosis etc..Apropos of oxymatrine injection,the short elimination half-life and poor distribution in liver result in low biological availability.With the development of nanotechnology,there has been a new magnetism drug-carried system mediated by nanovector.In the magnetic field,the system can implement site-specific targeting drug administration,which can raise drug concentration in targeting organ,elevate therapeutic effect.In the study,OM was used as model drug to prepare magnetic poly D,L-lactide-co-glycolide oxymatrine nanoparticles(M-PLGA-OM-NP).Method1.M-PLGA- OM-NP were prepared by multiple emulsion-solvent evaporation process. We observe the shape of nanoparticles by transmission electron microscope(TEM), and evaluate the mean diameter,drug loading,entrapment efficiency,etc..2.Detect tissue distribution of M-PLGA-OM-NP in mice with magnetic field or not by high performance liquid chromatography-tandem mass spectrometry(LC-MS) method.3.By establishing models of dimethylnitrosamine(DMN)-induced liver fibrosis in mice, the expression ofα-smooth muscle actin(α-SMA) in the livers of mice was detected by immunohistochemical assay and the score of liver fibrosis in liver pathology was determined by H&E staining and Van Gieson staining. Result1.M-PLGA-OM-NP was prepared successful.The shape of nanoparticles was observed, the nanoparticles had regular spherical surfaces.The mean diameter of the nanoparticles were 146.5nm.The mean drug loading and entrapment efficiency were 7.61%and 44.8%respectively.2.After injecting M-PLGA-OM-NP,no matter magnetic field was provided or not,the drug concentration of liver was higher than that of normal of OM solution.Using magnetic field,the drug concentration of liver was siganifically elevated than the other two groups.3.Compared to model group there were a decline of serum ALT in M-PLGA-OM-NP group(P＜0.001).Microscopy revealed there were wild septa expansions from portal area to central venous,piecemeal and confluent necrosis and there was pseudo-nodular formation in part of the lobular in model group,while in M-PLGA-OM-NP group these lesions were much improved.The expression ofα-SMA in liver tissue was decreased in M-PLGA-OM-NP group.There were no difference between NP group and model group in the level of serum ALT and liver pathological changes.Conclusions1.The method for preparing M-PLGA-OM-NP is simple and can meet the requirement of pharmaceutics.2.M-PLGA-OM-NP can elevate the drug concentration of liver in mice.By magnetic field,the nanoparticles can obviously elevate the drug concentration of targeting organ.3.In the field of magnetic,the nanoparticles could reinforce the prophylactic effect of oxymatrine in DMN-induce mice experimental liver fibrosis.