摘要Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify the structure of mannose.Glycyr-rhetinic acid-tanshinone lipid nanoparticles(GT-LN)and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles(GT-MLN)were prepared.The physicochemical properties and release profiles of both formulations were evaluated,and their pharmacokinetic behavior and tissue distribution were investigated.Results:The average particle sizes of GT-LN and GT-MLN were 190.20±1.35 and 204.83±3.86 nm,respectively,with corresponding surface Zeta potentials of-28.0±1.68 and-30.24±2.10 mV.The drug release profile of GT-LN conformed to the Higuchi equation,whereas that of GT-MLN followed both the first-order kinetic and Ritger-Peppas equations.Both formulations significantly enhanced the gastro-intestinal stability of the drug.In vivo studies in mice demonstrated that hepatic GA and TSN concen-trations in both groups were significantly higher than those in the original drug suspension group(P=.01).Notably,the concentrations in the GT-MLN group were significantly higher compared to the GT-LN group(P=.01).Conclusion:Man ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose.The Man ligand endowed these lipid nanoparticles with obvious active liver-targeting properties.Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.