Lymphatic Uptake and Biodistribution of Liposomes after Subcutaneous Injection I. Influence of the Anatomical Site of Injection

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Abstract
Liposomes have been proposed as carriers for the delivery of therapeutic and diagnostic agents to the lymphatic system. Subcutaneous (s.c.) injection is the route of administration most extensively studied for this purpose. To establish the influence of the anatomical site of s.c. injection on lymphatic uptake of liposomes, we have examined the pharmacokinetics and biodistribution of small (0.10 μm) [3H]-labeled liposomes administered at three different s.c. sites of the rat. Lymphatic uptake of liposomes from the s.c. site of injection, lymph node localization and biodistribution in liver, spleen and kidneys were highly dependent on the site of injection. s.c. injection into the dorsal side of the foot or in the footpad resulted in relatively high uptake of liposomes from the site of injection as compared to uptake from the s.c. injection site at the flank. Moreover, injection into the dorsal side of the foot or in the footpad resulted in relatively high levels of radioactivity in regional lymph nodes, liver and spleen. The observed differences in liposome disposition are attributed to differences in the structural organization of s.c. tissue. We conclude that lymphatic uptake and lymph node localization of liposomes after s.c. administration strongly depends on the anatomical site of injection. Therefore, the s.c. site of injection should be carefully considered when developing diagnostic and therapeutic approaches involving the lymphatic system by means of s.c. administration of liposomes.