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, and antihuman immunodeficiency virus activity of free dideoxycytidine (ddC) and liposomal ddC (L-ddC). We have found that L-ddC was more efficiently taken up than its free form by RAW 264.7 cells (a monocyte-macrophage cell line) (p < 0.01) while a comparable uptake was seen in U937 cells (a promonocytic cell line). In the rat, L-ddC accumulated preferentially in liver and spleen when injected intravenously (p < 0.01), and mostly in spleen when given intraperitoneally (p < 0.01). In contrast, 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 accumulation and its in vivo distribution in reticuloendothelial system (RES) tissues, we conclude that ddC in liposomal formulation is a promising anti-HIV agent with a targeted action on the RES, which is considered a reservoir for dissemination of virus to other cells, tissues, and organs.
Makabi-Panzu
B
B
Laboratoire et Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
Lessard
C
C
Perron
S
S
Désormeaux
A
A
Tremblay
M
M
Poulin
L
L
Beauchamp
D
D
Bergeron
M G
MG
D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D004337:Drug Carriers; D005260:Female; D006678:HIV / Q000187:drug effects*; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D016047:Zalcitabine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D004337:Drug Carriers; D008081:Liposomes; D016047:Zalcitabine