Glycyrrhetinic acid-cyclodextrin grafted pullulan nanoparticles loaded doxorubicin as a liver targeted delivery carrier

Abstract

In this work, glycyrrhetinic acid (GA)-β-cyclodextrin grafted pullulan (GCDPu) was synthesized and used to form nanoparticles for liver-specific drug delivery. GCDPu was characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H NMR). The self-aggregated nanoparticles (GCDPu NPs) with a spherical dimension of about 200 nm were prepared and analyzed by dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM). Doxorubicin (DOX) was selected as an anti-cancer model drug, and the drug-loaded GCDPu NPs were prepared by the emulsion solvent evaporation method. Moreover, the drug loading efficiency (LE%) and loading content (LC%) were determined. Slow DOX release from DOX/GCDPu NPs was confirmed. GCDPu NPs were cytocompatible with Bel-7404 cells and showed high cellular uptake according to the MTT assay, confocal laser scanning microscope (CLSM) and flow cytometry (FCM) results. Compared with free DOX, DOX/GCDPu NPs have exhibited a longer half-life time (t1/2) and a larger area-under-the-curve (AUC). GCDPu NPs significantly increased DOX contents in the liver and decreased in heart and kidney. Furthermore, DOX/GCDPu NPs exhibited a better anticancer therapeutic effect on tumor-bearing mice. These findings suggest that GCDPu can serve a liver-specific drug delivery system.