Repeated injections of PEG-PE liposomes generate anti-PEG antibodies.
Liposomes containing the polyethylene glycol (PEG) derivative of phosphatidyl ethanolamine (PE) have recently been found to be promising drug carriers, as they facilitate controlled and target-oriented release of therapeutics. They also reduce the side effects of many drugs. Here, we present the results of a study on antiliposomal properties of rabbit sera obtained after weekly injections of small liposomes containing 20% PEG-PE. The effect was analysed as the level of induced carboxyfluorescein release from these liposomes in vitro. The incubation of liposomes with rabbit serum taken after the injections induced the release of carboxyfluorescein at a higher level than was seen for incubation with untreated animal's serum. The strongest effect was observed for serum obtained after the second injection, i.e. during the second week of the study. The effect was much smaller after the serum samples were preheated at 56 degrees C. The binding of serum proteins by PEGylated liposomes was analysed via gel filtration and via the immunoblot technique using goat anti-rabbit IgG; this revealed that the serum protein which bound to the liposomes in vitro had a molecular weight of 55 kD and reacted with the anti-IgG antibody. Competition with PEG or lipids indicate that this IgG has an anti-PEG activity. We therefore assume that these antibodies are responsible for the activation of complement and leakage induction of PEG-liposomes. Such antibodies could be responsible for increased phagocytosis by RES macrophages (in particular liver macrophages) and decreased circulation time.
Sroda
Kamila
K
Academic Centre for the Biotechnology of Lipid Aggregates, Przybyszewskiego 63/77, 51-148 Wrocław, Poland. afsbc@ibmb.uni.wroc.pl
Rydlewski
Janusz
J
Langner
Marek
M
Kozubek
Arkadiusz
A
Grzybek
Michał
M
Sikorski
Aleksander F
AF
D000818:Animals; D005452:Fluoresceins / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology*; D008081:Liposomes / Q000276:immunology* / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000276:immunology*; D011092:Polyethylene Glycols; D011817:Rabbits; D013997:Time Factors
D005452:Fluoresceins; D007074:Immunoglobulin G; D008081:Liposomes; D010714:Phosphatidylethanolamines; C024098:6-carboxyfluorescein; D011092:Polyethylene Glycols