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  • Title: The in vitro characterisation and biodistribution of some non-ionic surfactant coated liposomes in the rabbit.
    Author: Khattab MA, Farr SJ, Taylor G, Kellaway IW.
    Journal: J Drug Target; 1995; 3(1):39-49. PubMed ID: 7655819.
    Abstract:
    The degree of adsorption of some novel silicone glycol copolymers onto polystyrene microspheres was studied and compared with the sorption onto small unilamellar vesicles (SUVs) composed of egg phosphatidylcholine (EPC) and prepared by the detergent dialysis technique. These non-ionic surfactants are 'comb' polymers of the ABn type where A is a silicone 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 chains. Upon incubation with SUVs, delta h of the different polymers was similar (3 nm) and significantly less (two sample t-test, p < 0.01) than the corresponding delta h on the polystyrene latex which could be attributed to the penetration of the polymers into the outer phospholipid 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. The highest retention (49% at 5 h) was obtained with SUVs coated with the silicone polymer possessing the highest glycol content and the longest ethylene oxide chains. Sterically stabilised vesicles were also formed by coating dipalmitoyl phosphatidyl-choline (DPPC)/cholesterol (Chol) (molar ratio 1:1) with two of these silicone glycol copolymers and Poloxamer 338. The liposomes were labelled with 67gallium-desferrioxamine (67Ga-DF). Incubation of radiolabelled Poloxamer 338-coated vesicles in saline or serum at 37 degrees C for 24 h resulted in less stable liposomes compared to the more stable non-coated or silicone coated vesicles. Following intravenous (i.v.) administration in rabbits, free 67Ga-DF rapidly disappeared from the circulation (half-life = 41.4 min) and accumulated in the bladder. Two populations of vesicles were prepared (136 +/- 2.9 nm and 100 +/- 1.4 nm). 24 h after i.v. injection 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 ethylene 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 was significantly reduced to 37% upon coating the liposomes with the silicone glycol copolymers. At 30 min post i.v. injection, approximately 10% of the activity was associated with the heart/lung region irrespective of liposome size or polymer coating.(ABSTRACT TRUNCATED AT 400 WORDS)
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