一般論文
Activity of Amphipathic Polyethyleneglycols to Prolong the Circulation Time of Liposomes
1999 年 59 巻 1 号 p. 32-42
詳細
1999 年 59 巻 1 号 p. 32-42
We have studied the reticuloendothelial-avoidance mechanisms of PEG liposomes in vivo and in vitro. Only relatively small liposomes (diameter < 200 nm) had their circulation time prolonged by the inclusion of amphipathic PEG. Increasing the size of PEG liposomes led to significant spleen uptake, probably via a filter mechanism. However, a study of the biodistribution in splenectomized mice showed that large-sized PEG liposomes have an intrinsic ability for long circulation in vivo. The presence of PEG reduced the distribution of liposomes into nonparenchymal cells in the liver. These results are consistent with the significantly reduced uptake of PEG liposomes by J774 cells, a murine macrophagelike cell line. The proteins associated with liposomes in vivo were analyzed by SDS-polyacrylamide gel electrophoresis and immunoblot analysis after isolation by using a spin column procedure. Data showed that PEG on the surface of liposome prevents the binding of complement 3 (C3) to the liposome. An in vitro experiment using an avidin-biotin agglutination assay of liposomes also showed that the PEG chains sterically block avidin-biotin binding. These studies suggested that PEG prolongs liposome circulation time by providing a strong steric barrier which prevents close contact with serum protein (complement) and RES cells (macrophages).
