Subcutaneous Administration of Liposomes for Lymphatic Targeting

Abstract

Liposomes have received considerable interest for targeting to regional lymph nodes after s.c. administration. Detailed information on factors influencing lymphatic uptake and lymph node localization of s.c. administered liposomes is, however, not readily available. The present paper provides a short overview of the outcome of recently performed studies on factors potentially affecting lymphatic disposition of liposomes after s.c. injection into rats. An important factor influencing lymphatic disposition was found to be the anatomical site of injection. S.c. injection into the dorsal side of the foot or in the footpad resulted in relatively high uptake (about 40% of the injected dose (%ID)) of small liposomes (mean size about 0.10 μm) from the site of injection compared to uptake from the s.c. injection site at the flank from which uptake was low (< 5 %ID). Liposome size was found to be the most important liposome characteristic influencing lymphatic disposition of s.c. administered liposomes. Small, liposomes (mean size about 0.04 μm) were taken up by the lymphatic system to a relatively high extent (about 74 %ID) compared to large, non-sized liposomes which remained present almost completely at the site of injection. Small liposomes were less efficiently retained by regional lymph nodes than larger liposomes. Liposomal lipid composition did not influence lymphatic disposition significantly with one exception: lymph node localization of liposomes was substantially enhanced by inclusion of phosphatidylserine into the liposomal bilayers. Remarkably, lymphatic uptake and lymph node localization was only slightly affected by distearoylphosphatidylethanolamine-poly(ethyleneglycol) (DSPE-PEG¹) mediated steric stabilization of the liposome surface. Studies designed to elucidate the intranodal fate of liposomes confirmed that liposomes are mainly taken up by lymph node macrophages. Small liposomes may also be taken up by other cells such as endothelial cells. In addition, it was found that PEG-liposomes retained by lymph nodes are also taken up by lymph node macrophages.