The fate of small (30-60 nm) and large (about 400 nm diameter)
liposomes composed of
phosphatidylcholine or
sphingomyelin and equimolar
cholesterol and containing quenched
carboxyfluorescein and 111In-labelled
bleomycin after footpad injection of rats was investigated. Judging from the values of latent
carboxyfluorescein in the plasma,
phosphatidylcholine and
sphingomyelin small
liposomes entered the blood circulation intact, presumably via the lymphatics to reach 3 h after injection a peak of 16.9 and 23.1% of the dose per total blood, respectively. Of the 111In radioactivity given in
phosphatidylcholine liposomes, about 32% was recovered in the liver. Hepatic uptake of 111In for
sphingomyelin liposomes was lower (about 9%) reflecting their slower rate of clearance. No latent
carboxyfluorescein could be detected in the blood after injection with
phosphatidylcholine or
sphingomyelin large
liposomes and levels of 111In in the liver (and spleen) were very low. A proportionally much greater amount of liposomal 111In was intercepted by the popliteal and to a lesser extent, the lumbar lymph nodes. Such uptake was significantly higher (e.g. 463%) for small than for large (e.g. 195% per g popliteal nodes)
liposomes. After foot pad injection of large
liposomes into Walker 256 tumour-bearing rats, localization of 111In in the popliteal nodes was similar to that seen with control animals. However, 111In localization in the lumbar nodes was augmented more than 5-fold. These results suggest that large
liposomes as used in this study, characterized by efficient
drug entrapment, inability to reach the liver and spleen and improved localization in the lymph nodes of tumour-bearing animals may be preferable to vesicles of small size for the local treatment of
lymphatic metastases.