Liver-targeted delivery of liposome-encapsulated curcumol using galactosylated-stearate.

Abstract

Liver-targeted drug delivery improves the efficacy of anti-liver cancer agents and reduces systemic toxicity by limiting the bioavailability of these drugs to within tumors. Liver targeting reagents with galactose residues, which selectively combine to asialoglyco protein receptors, have previously been used to improve liposome-encapsulated drug accumulation within liver cells. They lead to a reduction in liver cancer cell growth and have been used to cure certain hepatic diseases. In the present study, curcumol, which is the primary active component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in galactosylated-liposomes to enhance its anti-liver cancer efficacy. Galactosylated-liposomes and normal liposomes were labeled with propidium iodide. Galactosylated-liposomes with increasing concentrations of galactosylated-stearate (Gal-s) had a notably increased level of uptake in HepG2 cells (hepatoblastoma) compared with SGC-7901 (gastric cancer) and A549 (non-small cell lung cancer) cells. When the percentage of Gal-s reached 20%, liposome uptake plateaued. In the in vitro anti-liver cancer experiment, the anti-liver cancer efficacy of galactosylated-curcumol-liposomes increased significantly more compared with normal curcumol liposomes and free curcumol as indicated by cell survival rate and lactate dehydrogenase release rate. Collectively, these results demonstrate that galactosylated-liposomes are able to enhance the in vitro liver-targeting effect and anti-liver cancer efficacy of curcumol.