Targeted Drug Delivery Systems And Their In Vivo Behavior Of A Block Copolymer Liver Clove Gentiopicroside

One of which will be made of the biodegradable nanoparticles is one of effective dosage form. The aim of this study was to explore Polyethylene glycol-modified-polylactic polyglycolic acid copolymer (PEG-PLGA) as the carrier of the nanoparticles SYR material preparation, morphological characteristics and the body of drug release characteristics.1. Process research and formulation of SYR-PEG-PLGA nanoparticles The nanoparticles particle size, entrapment efficiency, drug loading as the evaluation index, investigation method and orthogonal design with the^proc essand formulation optimization of single factor. The optimization resu Its showthat, with the PEG-PLGA block copolymer as carrier material, poloxamer188as stabilizer, using double emulsion method for preparing SYR-PEG-PLGA nanoparticles (SYR-NPs) solution appearance with light blue mil k, packagesealing rate and total doses were (48.8±1.26)%and (11.01±0.39)%; particle size (87.69±0.39) nm, Zeta potential was-35.7±2.46m V. Subsequently, inappearance, solubility and particle size as the evaluat ion index, by means of comparison of process research, freeze-dried resu Its show, the concentration of3%trehalose as a white powder the freez e-drying protective agent SYR-NPs appearance is loose, solubility is goo d; compared with before lyophilization, entrapment efficiency, loading n o change in dosage, Zeta potential, particle size increases slightly, but s till less than90nm. After the show, good reproducibility, the process is feasible.2.Study on pharmacokinetics and biodistribution of SYR-NPsWith SYR saline solution as control group, pharmacokinetic parameters of SYR-NPs medicine, through the tail vein of the rats was injected int o the bloodin the design time of orbit determination of plasma concentrat ion of SYR,HPLC,3P97software was used to process the data, pharmaco kineticparameters fitting medicine. The results show that, nanoparticles gr oupconcentration time course is consistent with two compartment mode1. In the same dose, compared with saline group, SYR-NPs group significa ntly extended in rats in vivo Tl/2alpha and Tl/2beta, AUC, plasma clea rance rate increased, the results showed that the drug made of nano form ulations,prolong the action time of drug in vivo, make the body of dru g utilization andbiological utilization degree has been greatly improved.3.SYR-NPs study on pharmacodynamicsTo establish the rat acute liver injury model induced by^D-GalN, th e analysis of serum ALT, AST activity in semi automatic biochemical an alyzer, optical microscope HE staining pathological section, the hepatoprot ective effects ofnanoparticles. The results show that, the medicine group c an reduce the ALT,AST activity in serum, can improve the liver tissue d amage. Nanoparticles group and SYR group can obviously reduce the live r tissue degeneration andnecrosis, and inflammatory reaction, and nanoparti cles has more significant effect, indicating that SYR-NPs has protective e ffect on rats with acute liverinjury induced by D-GalN.4.Study on the antitumor activity of SYR-NPs in vitroMTT method was used to study nanoparticle toxicity on HepG2.2.15cells,results showed that, the free drug group and nanoparticles can inhibit the proliferation of HepG2.2.15cells, and with the increase of drug concentrationthe inhibition rate increase; the same concentration of inhibition of each drugrate increased as time goes on; nanoparticles group with incubation time prolonged, the inhibition rate gradually increased and reached the level ofinhibition of free drug, showed that the nanoparticles group had obvioussustained release effect.SYR-NPs prepared in this study successfully, the spherical and unifor m,particle size of less than90nm, with a narrow particle size distributio n; release in vitro conformed to Higuchi equation, with sustained releas e property; in rats in vivo clearance is slower, prolonged circulation time in vivo, have certain effect in long cycle; in vivo distribution has liver tar geting effect. The prevention of obvious protective effects on rats with a cute liver injury induced by D-GalN; has inhibitory effect on the prolifer ation of HepG2.2.15cells.