COMPARISON OF CELLULAR ACCUMULATION, TISSUE DISTRIBUTION, AND ANTI-HIV ACTIVITY OF FREE AND LIPOSOMAL 2',3'-DIDEOXYCYTIDINE

We have investigated the cellular accumulation, tissue distribution, a nd antihuman immunodeficiency virus activity of free dideoxycytidine ( ddC) and liposomal ddC (L-ddC). We have found that L-ddC was more effi ciently taken up than its free form by RAW 264.7 cells (a monocyte-mac rophage cell line) (p < 0.01) while a comparable uptake was seen in U9 37 cells (a promonocytic cell line). In the rat, L-ddC accumulated pre ferentially in liver and spleen when injected intravenously (p < 0.01) , and mostly in spleen when given intraperitoneally (p < 0.01). In con trast, free ddC was rapidly eliminated out of the body. Liposomal ddC showed a similar anti-HIV activity in comparison with free ddC in U937 cells. Given the fact that encapsulation of ddC in liposomes does not affect its anti-HIV activity but enhances its in vitro cellular accum ulation and its in vivo distribution in reticuloendothelial system (RE S) tissues, we conclude that ddC in liposomal formulation is a promisi ng anti-HIV agent with a targeted action on the RES, which is consider ed a reservoir for dissemination of virus to other cells, tissues, and organs.