Study On Diosmetin Solid Lipid Nanoparticles Oral Preparation

Diosmetin?Dios?is a kind of flavonoids widely distributed in the plant kingdom.It has many pharmacological effects,such as anti-bacterial,anti-oxidation,anti-inflammatory,prevention of osteoporosis,protection of vision and anti-tumor.It has great research value and potential.Due to its low oral bioavailability,it restricts the clinical application of Dios.This project uses Dios as a model drug and palmitic acid as a lipid carrier to design a Diosmetin-solid lipid nanoparticle?Dios-SLN?oral drug delivery system to improve the oral bioavailability of Dios;In addition,the formulation process of Dios-SLN was optimized,and the in vitro release rules of Dios-SLN,the pharmacokinetic characteristics in rats,and the tissue distribution in mice were investigated.This topic is mainly studied from the following aspects:Dios-SLN was prepared by solvent injection method,and its encapsulation efficiency was determined by dextran gel chromatography.Particle size and entrapment efficiency were used as indexes.The effects of different lipids,different surfactants,lecithin and lipid ratio,drug lipid ratio,drug loaded lipid concentration and surfactant concentration on the performance of Dios-SLN were investigated by single factor.On the basis of single factor investigation,palmitic acid concentration,brij78p concentration and drug lipid ratio were determined as the main factors.Entrapment efficiency was used as the index.The prescription of Dios-SLN was optimized by box Behnken response surface methodology,and the results were analyzed.The optimal prescription was:surfactant concentration 3.39%,palmitic acid concentration 0.116%,drug lipid ratio 21:100,lecithin:palmitic acid 1:1.Three batches of Dios-SLN samples were prepared under the optimum conditions.The results showed that the average values of entrapment rate and drug loading were 95.13±1.05%?n=3?and 9.04±0.12%?n=3?,respectively.The particle size was 91.73±3.18 nm?n=3?.The quality of the product was stable and the repeatability was good.PBS?pH7.4?+0.75%brij78p was used as dialyzing medium to investigate the release of Dios SLN in vitro.Mathematical models such as zero order kinetic equation,first order kinetic equation,Higuchi equation and biexponential equation were used to fit the cumulative release of Dios-SLN,among which the biexponential model had the best fitting effect and sustained-release function.In the pharmacokinetic study of Dios SLN rats in vivo,the concentration of Dios in plasma was measured after intragastric administration of Dios solution and Dios-SLN solution,and the data were analyzed with DAS2.0 pharmacokinetic software.The area under the mean drug time curve of Dios group and Dios-SLN group AUC_0-t was28.963 mg/L*h,76.578 mg/L*h,AUC_0-?was 33.080 mg/L*h,90.093 mg/L*h,indicating that Dios SLN can improve the oral bioavailability of Dios.After the mice were administrated Dios and Dios-SLN respectively by intragastric administration,the concentration of Dios in each tissue was detected.It was found that Dios was distributed in each tissue,and the liver content of Dios-SLN group was higher,indicating that Dios-SLN had liver targeting effect.The results of this study show that Dios-SLN prepared with palmitic acid as a lipid material and Brij78P as a surfactant has a simple process and good repeatability;pharmacokinetic results show that Dios is made into solid lipid nanoparticles after oral absorption The bioavailability has been significantly improved;the results of mouse tissue distribution studies have shown that Dios-SLN has a liver-targeting function,which achieves the purpose of experimental design and provides experimental basis for the development of Dios preparations.