Design And Preparation Of Usnic Acid Lipid Microspheres Drug Loading System System And Study On Pharmacokinetics

Usnic acid（UA）,as two benzofuran antibiotics,is the main chemical components of usnic,UA belongs to the non genotoxic anticancer agent,and it is a potential new drug candidate for cancer chemotherapy.UA holds extensive pharmacological effects,such as anti-inflammatory,antioxidant,antibacterial,antiviral and antitumor and other pharmacological activities.The objective of the study was the preparation of usnic acid lipid microsphere system.（1）HPLC was established for the determination of UA.The C₁₈（250 mm?6 mm,5?m）was used with the mobile phase consisting of methanol-(50 mmol.L^-1:KH₂PO₄trimethylamine)（70:30）at a flow rate of 1 mL·min^-1.UV detection wavelength was set at 285 nm,and the temperature was at 40℃.its linearlion with concentration(C,μg·m L^-1)as abscissa,peak area（A）is vertical to regression equation:A=79.807C+29.351,the correlation coefficient r=0.9996,flurbiprofen axetilconcentration in 0.20²5.05μg·mL^-1 had good linear relationship with the peak area,The results show that the method is simple,reliable and reproducible,and can be used for the determination for UA.Usnic Acid’s oil/water distribution coefficient logP is 2.94.（2）Optimization of the preparation and the prescription of UA lipid microsphere.The optimized preparation was two step high pressure homogenization;the optimizati-on prescription as follows 0.45%,LCT 6.25%,MCT 6.25%,yolk lecithin 5%,glycerol2.5%,oleic acid 0.7%and VE 0.5%.The oil phase and water phase were heated to65℃and 70℃respectively,Then the two phases were mixed to form a coarse emulsion by using high-speed shearing at 16800 r·min^-1 for 10 min,pH of coarse emulsions was adjusted to 5⁷.High pressure homogenization pressure was 80 Mpa for 6 times,the sterilization condition was 115℃for 30 min.（3）To study the physicochemical properties and stability of UA lipid microspher-es.The appearance of UA lipid microspheres was milky white,without oil droplets,hanging wall and stratification.The lipid microspheres were spherical with uniform dispersion and smooth surface,without any adhesion according to TEM.The content of UA was 98.9%,the entrapment efficiency was（80.50±0.13）%,pH of UA was（6.7±0.4）,the particle size was 237 nm,the PI was 0.137,and Zeta potential-39.0 mV,The appearance,particle size,Ke and pH of the lipid microsphere swere stable for 10days at 4℃,20℃,and（4500±500）lx.（4）The study of pharmacokinetics and tissue distribution of UA lipid microspheres.The concentrations of UA in plasma and tissue were determined by HPLC at different time points.The pharmacokinetic parameters were calculated by the DAS 2.0 software.Compared with suspension group,the main pharmacokinetic parameters of lipid microsphere:AUC_0-t and AUC_0-∞increased significantly 1.62times（p<0.01）,1.60 times（p<0.01）,the relative bioavailability were 159.82%,C_maxax were increased obviously 1.37 times（p<0.05）,t_1/2 and CL decreased by 21.25%（p>0.01）,35.13%（p<0.05）.The results showed that the peak time of T_max=0.145 h was relatively delayed,the absorption of drugs increased,and the bioavailability of drug improved.The tissue distribution showed that the drug concentration in the liver was the highest after intravenous injection,indicating that the drug may be metabolized mainly in the liver.Lipid microspheres can improve the distribution of drugs in the liver,kidney and heart.As a result,UA lipid microspheres has changed distribution of drugs in various tissues.This study provides a theoretical basis for the development and design of new drug dosage forms.