New synthetic amphiphilic polymers for steric protection of liposomes in vivo

• Published in: Journal of pharmaceutical sciences Vol. 84; no. 9; p. 1049
• Main Authors: Torchilin, V P, Trubetskoy, V S, Whiteman, K R, Caliceti, P, Ferruti, P, Veronese, F M
• Format: Journal Article
• Language: English
• Published: United States 01-09-1995
• Subjects: Animals; Detergents; Liposomes - chemistry; Liposomes - pharmacokinetics; Liver - metabolism; Mice; Molecular Weight; Morpholines - chemical synthesis; Morpholines - chemistry; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polymers - chemical synthesis; Polymers - chemistry; Povidone - chemical synthesis; Povidone - chemistry; Tissue Distribution
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600840904

Carboxy group-terminated synthetic polymers--branched poly(ethylene glycol), poly(acryloylmorpholine), and poly(vinylpyrrolidone)--were made amphiphilic by derivatization with phosphatidyl ethanolamine via the terminal carboxy group and then incorporated into lecithin-cholesterol liposomes prepared by the detergent dialysis method. Following the biodistribution of liposomes in mice, all three polymers were shown to be effective steric protectors for liposomes and were able to sharply increase liposome circulation times in a concentration-dependent manner. The accumulation of liposomes in the liver decreases. The effects observed are similar to those found for liposomes modified with linear poly(ethylene glycol). At low polymer concentration, amphiphilic branched poly(ethylene glycol) seems to be the most effective liposome protector, most probably, because at the same molar content of anchoring groups, each attachment point carries two polymeric chains and doubles the quantity of liposome-grafted polymer comparing to linear poly(ethylene glycol).