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In vitro antiproliferative activity of a medium-chain triglyceride solution of 1,25-dihydroxyvitamin D3 in HepG2
M H Pourgholami1, J Akhter, D L Morris
1University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia.
Background:
Successful targeted delivery of 1,25-dihydroxyvitamin D3 [1,25-D3] for the treatment of liver cancer would necessitate the use of an appropriate delivery agent.
Materials And Methods:
Using liver cancer cell line HepG2 in culture, we examined, the possibility of using medium-chain triglyceride (MCT) as a solvent for targeted delivery of 1,25-D3. The drug was made up in either the medium or first dissolved in MCT and subsequently diluted in the medium. Cells were exposed for 1 (acute) or 5 days (chronic) to the 2 different formulations of the drug and cell proliferation was measured by [3H]thymidine and cell count methods.
Results:
In chronic experiments, exposure of cells to the MCT containing formulation of 1,25-D3 led to significantly greater inhibition of cell proliferation. In the acute experiments where, 1 day 1,25-D3 treatment was followed by 4 days of incubation with normal medium (no drug, no MCT), inhibition of proliferation was more than 2 fold greater in cells exposed to the 1,25-D3/MCT preparation.
Conclusion:
These results indicate that, 1,25-D3 dissolved in MCT probably accumulates and then acts as a sustained release drug depot formulation, in which case it may have potential for the regional treatment of liver tumors.