Pourgholami M H, Akhter J, Morris D L
University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia.
Anticancer Res. 2000 Nov-Dec;20(6B):4257-60.
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.
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.
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.
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.
成功靶向递送1,25 - 二羟基维生素D3[1,25 - D3]用于治疗肝癌需要使用合适的递送剂。
利用培养的肝癌细胞系HepG2，我们研究了使用中链甘油三酯（MCT）作为1,25 - D3靶向递送溶剂的可能性。药物要么制成培养基制剂，要么先溶解于MCT，随后在培养基中稀释。细胞分别暴露于该药物的两种不同制剂1天（急性）或5天（慢性），并通过[3H]胸腺嘧啶核苷和细胞计数法测量细胞增殖。
在慢性实验中，细胞暴露于含MCT的1,25 - D3制剂导致对细胞增殖的抑制作用显著增强。在急性实验中，先用1,25 - D3处理1天，然后在正常培养基（无药物、无MCT）中孵育4天，暴露于1,25 - D3/MCT制剂的细胞增殖抑制作用增强超过2倍。
这些结果表明，溶解于MCT的1,25 - D3可能会蓄积，然后作为一种缓释药物制剂起作用，在这种情况下它可能具有用于肝脏肿瘤局部治疗的潜力。
