Liposome disposition in vivo IV: the interaction of sequential doses of liposomes having different diameters.

In order to evaluate the degree to which liposomes of the same composition but of different size interact with organ binding sites, a series of pre-dose studies have been carried out in mice. Two sizes of multilamellar liposomes were used: large (L) liposomes averaging 0.5 micrometer in diameter and small (S) liposomes averaging 0.06 micrometer in diameter. Lipid composition was phosphatidylcholine/phosphatidic acid/cholesterol/alpha-tocopherol in the molar ratio 4:1:5:0.1. Experiments consisted of a saturating pre-dose of either non-radioactive L- or S-liposomes followed at various times by a test dose of radioactively labelled L- or S-liposomes. When pre-dose and test dose were of the same diameter, an interaction was observed. A pre-dose of L-liposomes also interacted with a test dose of S-liposomes but a pre-dose of S-liposomes did not interact with a test dose of L-liposomes. All disposition effects were reversible, returning to control values within 24 h. These results indicate that L- and S-liposomes of identical composition may associate with different hepatic binding sites and that a class of non-specific binding sites available to S-liposomes but not to L-liposomes may exist.