Enzyme-catalyzed synthesis of mannose ester and its enhancement of tanshinone and glycyrrhetinic acid lipid nanoparticles

To improve the efficiency of drug delivery, a mannose vinyl stearate mannose ligand (Man ligand) with active liver-targeting properties was synthesized. Non-aqueous enzymatic synthesis was used to modify the structure of mannose. Glycyrrhetinic 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. 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 gastrointestinal stability of the drug. In vivo studies in mice demonstrated that hepatic GA and TSN concentrations 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). 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.