The use of lipiodol and medium chain triglyceride as delivery agents for hepatic arterial administration of 1, 25-dihydroxyvitamin D3--a potential new treatment for hepatocellular carcinoma.
It is well established that 1, 25 dihydroxyvitamin D3 is capable of inhibiting the proliferation of a number of human cancer cell lines, including hepatoma cell lines. However, clinical usage in the treatment of cancers has been limited by its hypercalaemic effects. We hypothesised that by delivering 1, 25 dihydroxyvitamin D3 dissolved in a lipid based carrier agent as a hepatic arterial infusion it would be possible to achieve high local concentrations within hepatomas for prolonged periods, whilst avoiding high systemic concentrations and hypercalcaemia. We examined this hypothesis by administering a hepatic arterial infusion of 1, 25 dihydroxyvitamin D3 in either Lipiodol, Medium Chain Triglyceride (MCT), or saline to hepatoma bearing rats. Assay of serum and tissue concentrations revealed that this approach using lipiodol or triglyceride results in selective distribution of 1, 25-dihydroxyvitamin D3 into, and retention within hepatoma tissue and low initial systemic serum levels. Lipiodol was more effective in these respects than MCT. This method of administration has potential in the treatment of hepatoma.
Finlay
I G
IG
University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Sydney, Australia.
Stewart
G J
GJ
Pourgholami
M H
MH
Akhter
J
J
Morris
D L
DL
D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D014280:Triglycerides; D007459:Iodized Oil; D002117:Calcitriol