In vitro antiproliferative activity of a medium-chain triglyceride solution of 1,25-dihydroxyvitamin D-3 in HepG2 cells

Background: Successful targeted delivery of. 1,25-dihydroxyvitamin D-3 [1,2 5-D-3] far the treatment of liver cancer would necessitate the use of an ap propriate delivery agent Materials and Methods: Using liver cancer cell lin e HepG2 in culture, we examined the possibility of using medium-chain trigl yceride (MCT) as a solvent for targeted delivery of 1,25-D-3. The drug was made lip in either the medium or first dissolved in MCT and subsequently di luted in the medium. Cells were exposed for 1 (acute) or 5 days (chronic) t o the 2 different formulations of the drug and cell proliferation was measu red by [H-3]thymidine and cell count methods Results: In chronic experiment s, exposure of cells to the MCT containing formulation of 1,25-D-3 led to s ignificantly greater inhibition of cell proliferation. In the acute experim ents where, 1 day 1,25-D3 treatment was followed by 4 days of incubation wi th normal medium (no drug no MCT), inhibition of proliferation was more tha n 2 fold greater in cells exposed to the 1,25-D-3/MCT preparation. Conclusi on: These results indicate that, 1,25-D-3 dissolved in MCT probably accumul ates and then acts as a sustained release drug depot formulation, in which case it may have potential for the regional treatment of liver tumors.