Harvie P, Désormeaux A, Gagné N, Tremblay M, Poulin L, Beauchamp D, Bergeron M G
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
AIDS. 1995 Jul;9(7):701-7. doi: 10.1097/00002030-199507000-00006.
To improve the pharmacokinetics and lymphoid tissues targeting of 2',3'-dideoxyinosine (ddI) by encapsulation in liposomes.
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).
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.
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.
通过脂质体包封提高2′,3′-双脱氧肌苷（ddI）的药代动力学及淋巴组织靶向性。
在C57BL/6小鼠静脉注射和皮下注射单次大剂量（3 mg ddI/kg）后，测定游离及脂质体包封的ddI的药代动力学和组织分布。
静脉注射脂质体包封的ddI极大地降低了抗HIV药物的全身清除率。包封于112 nm和83 nm脂质体中的ddI的血浆消除半衰期分别比游离药物高46倍和14倍。脂质体脂质的组织分布情况清楚地表明，静脉注射后，脂质体能够有效地靶向淋巴结及富含巨噬细胞的组织（脾脏和肝脏）至少24小时。相比之下，皮下给药后脂质体在这些组织中的蓄积要低得多。
脂质体包封ddI极大地改善了静脉注射后抗HIV药物的药代动力学。脂质体的应用可能是一种靶向淋巴组织的便捷方法。旨在提高药物在脂质体内滞留的策略应能进一步增强并延长药物向淋巴器官的递送。
