In vitro antiproliferative activity of a medium-chain triglyceride solution of 1,25-dihydroxyvitamin D3 in HepG2 cells.
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.


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.


CONCLUSIONS
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.
Pourgholami
M H
MH
University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia.
Akhter
J
J
Morris
D L
DL
D002117:Calcitriol / Q000008:administration & dosage*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014280:Triglycerides / Q000008:administration & dosage* / Q000737:chemistry; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004338:Drug Combinations; D014280:Triglycerides; D002117:Calcitriol; D013936:Thymidine