Study On Ginsenoside Rg3 Nanopreparations Delivery Systems

Objective: To improve bioavailability and targeting property of ginsenoside Rg3,studying preparation technology of ginsenoside Rg3 liposomes, nanoparticles and microemulsions and the differences of tissue biodistribution in mice to compare various types of nano-preparations target specific.Methods:(1)Preparation of ginsenoside Rg3 liposomes:Liposomes were prepared by thin-film ultrasonic dispersion method.Single factor test to determine the concentration of lecithin,ratio of lecithin and cholesterol and solvent,through L9(34) orthogonal test experiment to take the ratio of lecithin and drug,the temperature of the preparation and the pH as factors,the entrapment efficiency as the index to optimize formulation and preparation process.(2)Preparation of ginsenoside Rg3 PLGA nanoparticles:Nanoparticles were prepared by nanoprecipitation method.Single factor test the ratio of PLGA,the species and concentration of surfactants,through L9(34) orthogonal test experiment to the ratio of PLGA,the concentration of drug,the ratio of organic phase and aqueous phase as factors,the entrapment efficiency as the index to optimize formulation and preparation process.(3)Preparation of ginsenoside Rg3 microemulsion:The formulation was optimized by measure the solubility of drug in excipients and pseudo-ternary phase diagram.Using central composite design-response surface methodology experimental to the mass fraction of oil phase,surface and cosurfactant as factors,the particle diameter,zeta potential and equilibrium solubility of drugs as the index,according to intuitive analysis and actual situation to determine the optimal prescription.(4)Tissue distribution:Mice tail vein injection of the same dose of three ginsenoside Rg3 nano-preparations,then taking different time points of mice heart,liver,spleen,lung,kidney and plasma,after playing homogenized the protein processing by using HPLC for the determinination of ginsenoside Rg3 in organizations of distribution.Results:(1)The optimum prescription and process conditions of ginsenoside Rg3 liposomes were as follows:the solvent was chloroform-ethanol(1∶1),the best weight ratio of lecithin to cholesterin and ginsenoside Rg3 was 4∶2∶1,the temperature was 50 ℃, and the pH of PBS was 6.8.The average particle size of liposomes was 111.8 nm with a potential of-38.67 mV,and the entrapment efficiency was 87.85%.(2)The optimum prescription and process conditions of ginsenoside Rg3 PLGA nanoparticles were as follows:the concentration of PLGA was 10 mg·mL-1,the concentration of Rg3 was 3 mg·mL-1,the ratio of organic phase and water phase was 1:3.The average particle size of nanoparticles was 186.1 nm with a potential of-29.56 mV,and the entrapment efficiency was 87.29%.(3)The process conditions of ginsenoside Rg3 microemulsion were as follows:the proportion of ethyloleate、EL35、PEG400 and water was 8.25:12:4.75:75.The average particle diameter of ginsenoside Rg3 microemulsion was 60.50 nm with a potential of-15.63 mV,and there was no any layered after centrifuging at 4000 r·min-1 for 10 min.(4)Tissue distribution:Three kinds of ginsenoside Rg3 nano-preparations in the liver,spleen,lung tissue concentrations were higher than ginsenoside Rg3 groups monomer. Ginsenoside Rg3 in heart,kidney distribution significantly reduced and blood drug concentrations were significantly decreased.Conclusions: The craft was feasible,stable and applicable for the preparation of three ginsenoside Rg3 nano-preparations. Three ginsenoside Rg3 nano-preparations have obvious lung,spleen and liver targeting in mice.