THE IN-VITRO CHARACTERIZATION AND BIODISTRIBUTION OF SOME NONIONIC SURFACTANT COATED LIPOSOMES IN THE RABBIT

The degree of adsorption of some novel silicone glycol copolymers onto polystyrene microspheres was studied and compared with the sorption o nto small unilamellar vesicles (SUVs) composed of egg phosphatidylchol ine (EPC) and prepared by the detergent dialysis technique. These non- ionic surfactants are 'comb' polymers of the AB(n) type where A is a s ilicone chain with n pendant polyglycol chains (B). Photon correlation spectroscopy was used to measure the adsorbed layer thickness (delta h) following polymer sorption from aqueous solutions. delta h on latex particles was a function of the length of the polymer hydrophilic cha ins. Upon incubation with SUVs, delta h of the different polymers was similar (3 nm) and significantly less (two sample t-test, p < 0.01) th an the corresponding delta h on the polystyrene latex which could be a ttributed to the penetration of the polymers into the outer phospholip id bilayer. The glycol chains of the silicone polymers are assumed to be in a helical and planar position. Efflux of 5(6)-carboxyfluorescein from EPC liposomes was increased by the presence of these polymers. T he highest retention (49% at 5 h) was obtained with SUVs coated with t he silicone polymer possessing the highest glycol content and the long est ethylene oxide chains. Sterically stabilised vesicles were also fo rmed by coating dipalmitoyl phosphatidyl-choline (DPPC)/cholesterol (C hol) (molar ratio 1:1) with two of these silicone glycol copolymers an d Poloxamer 338. The liposomes were labelled with (67)gallium-desferri oxamine (Ga-67-DF). Incubation of radiolabelled Poloxamer 338-coated v esicles in saline or serum at 37 degrees C for 24 h resulted in less s table liposomes compared to the more stable non-coated or silicone coa ted vesicles. Following intravenous (i.v.) administration in rabbits, free Ga-67-DF rapidly disappeared from the circulation (half-life = 41 .4 min) and accumulated in the bladder. Two populations of vesicles we re prepared (136 +/- 2.9 nm and 100 +/- 1.4 nm). 24 h after i.v. injec tion of the different formulations of the 100 nm liposomes in rabbits, 20 - 27% of the activity was retained in blood. The silicone polymer with the highest glycol content and the longest ethlylene oxide chains showed the longest half-life (21.4 h). Using gamma scintigraphy, the liver/spleen uptake of the 136 nm non-coated vesicles was 57% which wa s significantly reduced to 37% upon coating the liposomes with the sil icone glycol copolymers. At 30 min post i.v. injection, approximately 10% of the activity was associated with the heart/lung region irrespec tive of liposome size or poIymer coating. Tnese non-ionic polymers are therefore useful agents in preventing the MPS uptake of vesicles and demonstrated characteristics similar to the new 'stealth' vesicles.