The Preparation And Pharmacokinetic Study Of Isoliquiritigenin Nanostructured Lipid Carriers

[Object] In this study, Isoliquiritigenin was used as model drugs, which was prepared isoliquiritigenin nanostructured lipid carriers (ISL-NLC), and then physicochemical properties of the nanostructured lipid carriers was The particle size, entrapment rate, morphology, phase transformation and stability were determined. The in vitro release profile of ISL-NLC was studied. The pharmacokinetics behavior in rats after tail vein injection was studied and then the relevant parameters were calculated. By the research in vivo and in vitro, in order to achieve liver intracellular deliver medication.[Method] ISL-NLC was prepared by emulsion ultrasound methods. To establish a method of optimizing the formulation of ISL-NLC by central composite design-reponse surface methodology, according to the results of the single factor and the evaluation index of entrapment efficiency, drug loading, particle size. The morphology of ISL-NLC was screened by TEM. The particle size and Zeta potential was measured by particle size and Zetasizer Nano-ZS90 laser. The formulation of lyophilized ISL-NLC was optimized based on its appearance, color and dispersing properties. Phase change in nanostructured lipid carriers was studied by DTA. The stability of ISL-NLC was examined by the evaluation of appearance and entrapment efficiency. Entrapment efficiency of ISL-NLC was determined by the method of minicolumn centrifugation-HPLC. The in vitro release profile of ISL-NLC was studied using dynamic dialysis method. The pharmacokinetic parameters were calculated by DAS 2.0 computer program. Mice in vivo real time level of cell size was observed by fluorescence endoscopic laser confocal imaging system, then the level of cell size nanoparticles could deliver medication in the cell was discussed. And nanoparticle distribution in mice was evaluated by Re and RTE.[Results] The nanoparticle solution looked like transparent and weak yellow in color, with a little opalescence. The entrapment efficiency was (83.42±1.3)%, the drug loading was (6.96±1.2)% by the best prescription of ISL-NLC by central composite design-reponse surface methodology. TEM gave the morphology of ISL-NLC is round and smooth, average particle size(89.31±5.2)nm, the Zeta potential was (-30.1±0.5)mV. The concentration of 5% sucrose and 5% mannitol as a freeze-drying protective agent, freeze-dried ISL-NLC appearance was loose and white powder, solubility was good. Results of DTA indicated that there was a new phase generated in the ISL-NLC. The results showed that it has certain sustained release effects that nanoparticles in vitro drug release conformed to Weibull equation, the fitting coefficient R2 was 0.9874. In vitro accumulation released 70.12% in 72 hour. Pharmacokinetic parameters shows that the elimination half-life T1/2β of ISL was 2.84 times compared with control group, and AUC was 3.31 times compared with control group. ISL-NLC could significantly improve the distribution of ISL in the liver. It indicated ISL-NLC had a certain liver targeting property. With the extension of time, the nanoparticles by extracellular into the cell, the number increases gradually which had a positive correlation.[Conclusion] The ISL-NLC which was prepared by the emulsion ultrasound methods was in small and homogeneous size, good morphology and high entrapment rate. ISL-NLC could extend the time in vivo and play the role of slow releasing and improve the bioavailability of the drug. ISL-NLC can really promote the drug content in liver and could be targeted into the hepatocytes.