Ligand-free high loading capacity ursolic acid self-carried nanovesicles enable hepatocyte targeting via absorbing apolipoproteins

Abstract

Ursolic acid (UA), a natural pentacyclic terpenoid carboxylic acid that can exert a potent hepatoprotective activity, has been developed into various types of nanoparticles to improve its pharmacological effects, however, the phagocytosis of nanoparticles by Kupffer cells greatly limits its efficacy. Herein, UA/Tween 80 nanovesicles (V-UA) were constructed and despite its simple composition, it fulfills multiple functions simultaneously: UA served as not only an active ingredient in the nanovesicle drug delivery system, but also acts as part of the carrier to stabilize UA/Tween 80 nanostructure; with a molar ratio of UA to Tween 80 up to 2:1, the formulation possesses a significant advantage of higher drug loading capacity; relative to liposomal UA (Lipo-UA), a conditional cellular uptake and higher accumulation of V-UA in hepatocytes provide insights into the hepatocytes targeting mechanisms of this nanovesicles. Favorable hepatocyte targeting ability also facilitates the treatment of liver diseases, which was well validated in three liver disease models.