Study On Lipid Liquid Crystalline Nanoparticles Of Paeoniflorin

Paeoniflorin (Pae) is the main chemical composition.It belongs to monoterpene glycosides, has a good anti-inflammatory, analgesic, hypoglycemic, protect liver, anti-cancer effect. But the effect of Pae is very slow, according to the reference that when Pae was given by intragastric (ig) administration to the rats alone, the bioavailability of Pae is less than 0.4%. Lipid liquid crystalline nanoparticles (LLCN) are a new vehicle for drugs, and it can increase the drug through rate, increase the bioavailability and delay the release of drugs. This topic through the study of Paeoniflorin liquid crystalline nanoparticles preparation technology and the best prescription, and then studies the absortion kinetics of Pae-LLCN preparation in intestine and pharmacokinetics in vivo based on pharmacodynamics experiments.Whether alterting pharmacokinetics characteristic of drugs can have an influence on therapeutic effect or not? And all the above provides the experiment evidence for developing the new preparation of Pae-LLCN. The details are as follows:1. The study on the physical and chemical properties and stability of the Paeoniflorin. High performance liquid chromatography (HPLC) method was established to determine the content of paeoniflorin. And then, we investigated the oil-water partition coefficients in dufferent dissolants. The results show that paeoniflorin can prepare into the liquid crystalline nanoparticles.2. Preparation and characterization of Paeoniflorin liquid crystalline nanoparticles. Established the Pae-LLCN the method of encapsulation efficiency.Using encapsulation efficiency as index, the Pae-LLCN was prepared by spontaneous emulsification and ultrasonic method, and the prescription of Pae-LLCN was optimized by orthogonal design. The best parameters of preparation:the speed of 500 r/min, stirring time 4 h, continuous ultrasonic 5 min (80 W,10 times, each time interval of 25s, sample during the interval of 0 ℃ water bath). The optimal formulation was poloxamer-glycerol monooleate (1:10), paeoniflorin inventory (40 mg), and PBS solution (20 mL). By transmission electron microscopy and nanometer particle sizer for characterizing the morphology and particle size:Pae-LLCN for spherical particle size and uniform roundness well, the particle size of around 200 nm.3. Characteristic study in pharmacy of Paeoniflorin liquid crystalline nanoparticles. The research was conducted mainly including the pH value, leakage, stability and in vitro release.It showed that its pH and leakage rate were stable.Compared with the paeoniflorin, the Pae-LLCN has good stability with better sustained release in vitro.4. Study on the Paeoniflorin liquid crystalline nanoparticles in rats intestinal absorption. From in vitro turn gut sac method was used to investigate Pae-LLCN and Pae in different parts of the small intestine absorption.Results showed that the pae-LLCN and Pae was zero order absorption in the intestinal absorbtion and passive transport.Both compared, Pae-LLCN in different parts of the small intestine absorption were higher than in the absorption of Pae.Jejunum’s absorbtion was the best.5. Study on the Paeoniflorin liquid crystalline nanoparticles in rats in vivo pharmacokinetic. The pharmacokinetic chanacteristics of single dose intragastric (ig) of Pae-LLCN in rats were investigated compared with that of Pae solution, and the data were calculated by means of DAS software.The results showed that preparations and raw materials if curves were fitted to the two compartment model, the weight coefficient is 1/CC. In vivo clearance rate (CL/F, CL/F, L·h-1 · kg-1) were19.352 and 48.955; the elimination half-life (T1/2p, h) were 4.842 and 3.023, showed that the lipid liquid crystalline nanoparticles drug delivery carriers could significantly prolong the drug paeoniflorin effect in vivo, improve the bioavailability.