THE ROLE OF LIPOPROTEINS IN THE TRANSPORT AND UPTAKE OF CYCLOSPORINE AND DIHYDRO-TACROLIMUS INTO HEPG2 AND JURKAT CELL-LINES

Objectives: We wish to examine the role of lipoproteins in the transpo rt and cellular uptake of cyclosporine (CsA) and tacrolimus. Design an d methods: The distribution of tritiated CsA and tacrolimus among lipo proteins was determined in normo- and hypertriglyceridemic sera. The u ptake of these two drugs into HepG2 and JURKAT cell lines was assessed in the presence of various concentrations of low density lipoproteins (LDL). Results: Our data showed that about 60% of these drugs were tr ansported by high density lipoprotein in normolipidemic sera, while ab out 50-60% were carried by very low density lipoprotein in hypertrigly ceridemic sera. Almost 80% of CsA and 70% of tacrolimus entered HepG2 and JURKAT cells within the first hour of incubation in lipoprotein fr ee media. However, the uptake was decreased (CsA by 60% and tacrolimus by 40%) in the presence of LDL. Conclusions: Lipoproteins play a majo r role in the transport of CsA and tacrolimus, but not in their cellul ar uptake.