LYMPHOID-TISSUES TARGETING OF LIPOSOME-ENCAPSULATED 2',3'-DIDEOXYINOSINE

Objective: To improve the pharmacokinetics and lymphoid tissues target ing of 2',3'-dideoxyinosine (ddl) by encapsulation in liposomes. Metho ds: The pharmacokinetics and tissue distribution of free and liposome- encapsulated ddl were determined in C57BL/6 mice following intravenous and subcutaneous administration of a single bolus dose (3 mg ddl/kg). Results: Intravenous administration of liposome-encapsulated ddl grea tly reduced the systemic clearance of the anti-HIV agent. The eliminat ion plasma half-life of ddl incorporated in 112 and 83 nm liposomes wa s 46 and 14 times higher than that of the free drug, respectively. The tissue distribution profile of liposomal lipids clearly showed that t he use of liposomes allows efficient targeting of lymph nodes and macr ophage-rich tissues (spleen and liver) for at least 24 h following int ravenous injection. in contrast, the accumulation of liposomes in thes e tissues was much lower following subcutaneous administration. Conclu sion: Incorporation of ddl in liposomes greatly improved the pharmacok inetics 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.