Preliminary Study On Preparation And Attenuation Of Usnic Acid Nano-drug Delivery System

Usnic acid is one of the secondary metabolites widely distributed in lichens.It is a kind of natural antibiotic with dibenzofuran structure.It is a non-genotoxic anticancer agent with a wide range of biological activities,such as anti-inflammatory,anti-bacterial,anti-tumor,anti-tuberculosis,anti-virus and other pharmacological activities,but the poor water solubility is not conducive to the drug.In this paper,we studied the preparation of nano crystal delivery system of usnic acid,and the hepatotoxicity of two kinds of nano drug delivery system of usnic acid.?1?HPLC method for the determination of usnic acid was established.The chromatographic conditions were as follows:welchrom^?C₁₈ column?250 mm×4.6 mm,5?m?,methanol-(50 mmol·L^-1 KH₂PO₄:triethylamine=500:1)?70:30?mobile phase,285nm detection wavelength,1mL·min^-1 flow rate,40?column temperature.?2?Turpentine microspheres were prepared by two-step high-pressure homogenization method and characterized as follows:the appearance of the prepared usnic acid lipid microsphere was milky white,uniform and opaque liquid,and there were no obvious oil drops,wall hanging and stratification on the surface of the liquid;the nano crystal of turpentine was round,with clear boundary morphology and smooth surface.The results showed that the microspheres were in good shape without cracking,deposition and rancidity.The particle size is 237.4 nm,PDI is 0.251,zeta potential is-39.0mv,all of which meet the requirements of nanocrystalline preparation.Within six months,the particle size of usnic acid was in the range of 235.8-237.4 nm,the zeta potential was in the range of-33.2-39.0mv,the entrapment efficiency was in the range of 76.69-80.50%,and the drug content was in the range of 94.18-96.07%.The results showed that the rosin microspheres were stable at 4?.?3?The preparation methods of three kinds of usnic acid nanocrystals were compared and optimized.The best preparation method is ball milling;the best prescription is 1%usnic acid,1.4%poloxamer 188,1.4%polysorbate 80;the best preparation process is that the mass ratio of different diameter grinding beads??12.7 mm,?10 mm,?8 mm,?5 mm?is2:3:4:4,and the rotation speed of ball mill is 500 r·min^-1.?5?In this paper,two kinds of nanodrug delivery systems of usnic acid were studied.Using LC-MS/MS method,we studied the metabolomics of the two drug delivery systems in mouse stem cells.The results showed that compared with the raw materials of usnic acid,the two dosage forms of usnic acid nanocrystals and lipid microspheres could reduce the hepatotoxicity.