Preparation And Preliminary Targeting Of Puerarin Biodegradable Nanoparticles

Polybutylcyanoacrylate is a common drug carrier in nanoparticle drug delivery system.It has good biocompatibility and biodegradability,simple preparation,high drug loading and low toxicity.It can also penetrate blood brain barrier,and it is attracting more and more people’s attention.Phospholipid is amphipathic substance from nature,the physicochemical properties and bioavailability of the phospholipid are different from the original drug.After the drug and the phospholipid form phospholipid complex,lipid solubility was enhanced and the absorption of the drug in the body can be effectively enhanced,its bioavailability was altered significantly.Puerarin mainly was used in clinical treatment of angina,arrhythmia,myocardial ischemia,hypertension,cerebral infarction and other cardiovascular diseases.Because puerarin has poor oral absorption,low oral bioavailability,poor lipid solubility and water solubility,which seriously affects the development of puerarin drugs.According to the characteristics of puerarin,which was used as a model drug,the polybutylcyanoacrylate as a carrier,phospholipid as an adjuvant,this paper will study on the preparation of puerarin phospholipid complex,the preparation process and preparation evaluation of puerarin phospholipid nanoparticles,the primarily targeting of puerarin phospholipid nanoparticlesTaking puerarin phospholipid complex rate as evaluation index,single factor investigation was conducted to determine the optimal conditions for preparing phospholipid complex.The optimal conditions for the preparation of phospholipid complexes were as follows:the reaction solvent was absolute ethanol,the puerarin reaction mass concentration was 1.0 mg/mL,the ratio of puerarin to phospholipids was 1:2,the reaction temperature was 30℃,and the reaction time was 0.5 h.The puerarin phospholipid complex nanoparticles were prepared by the method of interfacial polycondensation.Nanoparticles and free drugs were separated by ultrafiltration centrifugation.The encapsulation efficiency and drug loading of the drug were determined by UV spectrophotometry.Taking the encapsulation efficiency and drug loading of the drug as indexes,the single factor was used to investigate the prescription and the preparation process.Based on this,orthogonal experiments were designed to optimize the preparation,and the preparation of puerarin phospholipid complex nanoparticles prepared by the optimal prescription technology was evaluated.The morphology of the particles was observed by transmission electron microscopy and atomic force microscopy.It was a solid ball structure with a round appearance,uniform size and good dispersibility.Laser particle size analyzer indicated the average volume of nanoparticles size was 115.1±3.45 nm,the average Zeta potential was-15.23 mV.The pH of the nanoparticles was 7.04,the entrapment efficiency was 90.03± 1.80%and the drug loading was 11.80±0.12%.The appearance,particle size distribution and encapsulation efficiency of puerarin phospholipid complex nanoparticles did not change for 20 days at 20℃.The release of nanoparticles in vitro was evaluated with PBS(pH7.4)containing a concentration of 20%ethanol.The release of nanoparticles was slow,and the release of the drug in vitro was in accordance with the Weibull model.Puerarin phospholipid complex nanoparticles were primarily targeted.The formulation group increased the concentration in mice brain,prolonged the retention time in vivo,and had brain targeting compared with the control group.In this study,puerarin phospholipid complex nanoparticles were prepared on the basis of puerarin phospholipid complex,which improved the water solubility and poor lipid solubility of puerarin,optimized the preparation process of puerarin phospholipid complex nanoparticles,and prolonged its residence time in mouse brain tissue and it was easy to penetrate the blood brain barrier and enhance brain targeting.The completion of this work will provide a reference for the development of therapeutic drugs for cardiovascular diseases.and lay the foundation for the development of puerarin based drugs in order to enrich the dosage form of puerarin.