Abstract
A liver-targeted drug delivery carrier, composed of chitosan/poly(ethylene glycol)–glycyrrhetinic acid (CTS/PEG–GA) nanoparticles, was prepared by an ionic gelation process, in which glycyrrhetinic acid (GA) acted as the targeting ligand. The formation and characterization of these nanoparticles were confirmed by FT-IR, dynamic light scattering (DLS) and zeta potential measurements. The biodistribution of the nanoparticles was assessed by single-photon emission computed tomography (SPECT), and the cellular uptake was evaluated using human hepatic carcinoma cells (QGY-7703 cells). The anti-neoplastic effect of the doxorubicin·HCl-loaded nanoparticles (DOX-loaded nanoparticles) was also investigated in vitro and in vivo. The results showed that the CTS/PEG–GA nanoparticles were remarkably targeted to the liver, and keep at a high level during the experiment. The accumulation in the liver was 51.3% at 3 h after injection; this was nearly 2.6 times that obtained with the CTS/PEG nanoparticles. The DOX-loaded nanoparticles were greatly cytotoxic to QGY-7703 cells, and the IC 50 (50% inhibitory concentration) for the free doxorubicin·HCl (DOX·HCl) and the DOX-loaded CTS/PEG–GA nanoparticles were 47 and 79 ng/mL, respectively. Moreover, the DOX-loaded CTS/PEG–GA nanoparticles could effectively inhibit tumor growth in H22 cell-bearing mice.
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