1,25-dihydroxyvitamin D3 dissolved in lipiodol produces a sustained antiproliferative effect in the human hepatoblastoma cell line HepG2.

The steroid hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has potential to be used as an anti-tumor agent, but its clinical application has been restricted by the strong systemic calcemic activity. Regional administration of the drug dissolved in lipiodol, might be a way of selectively delivering high concentrations of the drug to lipiodol avid tumor cells without causing systemic side effects. In acute (1 day treatment) and chronic (5 days treatment) experiments, efficacy of the drug dissolved in ethanol (control) or lipiodol and subsequently diluted in the culture medium was tested in vitro against the hepatoblastoma cell line HepG2. Using [3H]thymidine incorporation and cell count, antiproliferative effects of 1,25-(OH)2D3 dissolved in the two different solvents was compared. Microscopic examination of cells exposed to the lipiodol containing media revealed intra-cellular presence of the oil in abundance. Chronic treatment of cells with either formulation of 1,25-(OH)2D3 resulted in profound inhibition of cell proliferation. However, exposure of cells to 1,25-(OH)2D3 in lipiodol was followed by significantly greater and lasting inhibition of cell proliferation in both acute and chronic studies. These results indicate that, 1,25-(OH)2D3 dissolved in lipiodol probably acts as a sustained release drug depot formulation, in which case it could have some potential for the regional treatment of liver tumors.