| Solid lipid nanoparticles(SLN) were solid colloidal systems with natural orsynthetic lipid as drug carrier.They were novel and promising drug deliverysystems,which could be used for topical,oral and parenteral administration and hadthe advantages of ideal targeting effects,low speed of drug leakage,good physicalstability and low toxicity, etc. In this thesis, verbascoside (VER) as a model drug, onverbascoside solid lipid nanoparticles (VER-SLN) were studied for drug deliverysystem.An HPLC method with Methanol-Water as mobile phase was developed for thequantitative determination of verbascoside in VER-SLN,the flow rate was1.0mL·min-1,DAD detection wavelength was331nm,column temperature was roomtemperature;The linear range of verbascoside were5.0～20.0μg·mL-1(r=0.9991).Between day precision and intra day precision good,RSD were1.02%and1.33%.The average recoveries were100.7%,RSD was0.84%.Specificitytest showed no interference in the determination of excipients on drug content.For theformula design, provide a basis to determine process conditions.Accodring to the results of the pre-formulation study,VER-SLN was prepared byemulsion ultrasound dispersing method. Ultrasonic time and intensity were keyfactors for the preparation of SLN. A high drug loading SLN could be acquired withGlycerol glyceryl monostearate as lipid carrier, poloxamer188and Soybeanphospholipids as emulsifiers. Base on the study above, with the criteria ofencapsulation efficiency, orthogonal design experiments were performed to optimizethe process parameters,The optimal formulation was as follows：drug-to-lipid ratio of1:75, the amount of Glycerol glyceryl monostearate was0.6g, the amount ofpoloxamer188was0.5g and the amount of Soybean phospholipids was0.2g.The physicochemical property of VER-SLN was evaluated. The appearance wereexamined by transmission electron microscopy. The VER-SLN particle size and Zetapotential were measured through the Zeta PALS high resolution Zeta potential and particle size analyzer; Room temperature (25℃) and the refrigerator (4℃) to observethe change of different time of its appearance and stability;The drug loading andencapsulation rate of SLN was determined by low-temperature ultracentrifugation; Toestablish a HPLC method for the the content of VER-SLN in the release medium, thismethod is accurate, reliable. In vitro release behavior of verbascoside from VER-SLNin pH7.4phosphate buffe was investigated in contrast to verbascoside raw materialmedicine.The results indicated VER-SLN was regular, with the mean diameter of(109±17) nm，the Zate potential of (-23±0.91) mV, and the pH of6.53, EE of theoptimal formulation was96.66%, and DL of was2.27%. Results of the preliminarystability experiments showed that the VER-SLN could be kept the appearance ofclarification at4℃for15days. There were no significant changes in the average sizeand the Zate potential, and the stability of VER-SLN was good, but under thecondition of room temperature,7d stability.The results of vitro release showed that thedrug solution release was completed within8hours, the drug release rate ofVER-SLN was47.2%at4h and reached92.9%at48h. The drug release profile ofVER-SLN in vitro fitted well to the Weiball distribution.Adopt intraperitoneal injection CCl4preparation liver damage model,treatment7days with VER-SLN,determination ALT and AST in serum in mice and SOD activityand MDA content in Liver homogenate,determine to liver damage process ofVER-SLN influence by observing liver histop-athology.The experimental liver injuryin mice Shows that following the treatment with VER-SLN, AST and ALT activities,and the content of MDA in liver were obviously reduced; the activity of SOD in liverwas obviously increased. Furthermore, the pathological changes were also improvedsignificantly.
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