Liposomal modification with uronate, which endows liposomes with long circulation in vivo, reduces the uptake of liposomes by J774 cells in vitro.
For overcoming rapid removal of liposomes from the bloodstream, we developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In this current study, we examined the in vitro interaction of PGlcUA-liposomes with J774 cells derived from mouse macrophages. Liposomal association with J774 cells at 37 degrees C did not increase compared with the binding at 4 degrees C when liposomes were modified with PGlcUA. RES-avoiding ability was not specifically endowed by glucuronate but by uronates in general, since palmityl-D-galacturonide showed a similar effect on liposomal clearance in vivo and liposomal uptake in vitro. These facts indicate that modification of the liposomal surface with uronic acid derivatives endows liposomes with a long circulation time in the bloodstream by reducing their uptake by macrophages.
Namba
Y
Y
Research Laboratories, Nippon Fine Chemical Co. Ltd., Hyogo, Japan.
Oku
N
N
Ito
F
F
Sakakibara
T
T
Okada
S
S
D000818:Animals; D002478:Cells, Cultured; D005965:Glucuronates / Q000097:blood / Q000493:pharmacokinetics*; D006603:Hexuronic Acids / Q000493:pharmacokinetics; D008081:Liposomes / Q000378:metabolism / Q000493:pharmacokinetics*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats
D005965:Glucuronates; D006603:Hexuronic Acids; D008081:Liposomes; D010715:Phosphatidylglycerols; C065782:1-O-palmitylglucuronic acid; C007819:galacturonic acid; C030345:1,2-dipalmitoylphosphatidylglycerol