Lymphoid tissues targeting of liposome-encapsulated 2',3'-dideoxyinosine.
OBJECTIVE
To improve the pharmacokinetics and lymphoid tissues targeting of 2',3'-dideoxyinosine (ddI) by encapsulation in liposomes.


METHODS
The pharmacokinetics and tissue distribution of free and liposome-encapsulated ddI were determined in C57BL/6 mice following intravenous and subcutaneous administration of a single bolus dose (3 mg ddI/kg).


RESULTS
Intravenous administration of liposome-encapsulated ddI greatly reduced the systemic clearance of the anti-HIV agent. The elimination plasma half-life of ddI incorporated in 112 and 83 nm liposomes was 46 and 14 times higher than that of the free drug, respectively. The tissue distribution profile of liposomal lipids clearly showed that the use of liposomes allows efficient targeting of lymph nodes and macrophage-rich tissues (spleen and liver) for at least 24 h following intravenous injection. In contrast, the accumulation of liposomes in these tissues was much lower following subcutaneous administration.


CONCLUSIONS
Incorporation of ddI in liposomes greatly improved the pharmacokinetics of the anti-HIV agent after intravenous injection. The use of liposomes could represent a convenient approach to targeting lymphoid tissues. Strategies aimed at improving drug retention within liposomes should further enhance and prolong drug delivery to lymphoid organs.
Harvie
P
P
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
Désormeaux
A
A
Gagné
N
N
Tremblay
M
M
Poulin
L
L
Beauchamp
D
D
Bergeron
M G
MG
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016049:Didanosine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D006678:HIV / Q000187:drug effects; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008081:Liposomes; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D014018:Tissue Distribution
D000998:Antiviral Agents; D004337:Drug Carriers; D008081:Liposomes; D016049:Didanosine