BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 g Pluronics PEO PPO 瀏餐灤 PEG block copoly Block copolymer rbed micelles/nanoparticles (Stolnik et al. 1995) PEGylated carriers PEG chain PEG binds 2-3 water molecules per repeat unit o Causes PEGylated compounds to function as though they are 5-10 times larger than their true molar Observed in SEC and gel electrophoresis experiments PEG/ater 'shield can reduce activity of protein, but generally the increased circulation time makes up for this Theory of stealth particle repulsion of protein binding to carriers Theory of Halperin, building on previous analyses of Alexander/de gennes and Szleifer Lecture 15-stealth' particles 3 of 8BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 15 – ‘stealth’ particles 3 of 8 (Stolnik et al. 1995) Adsorbed PEG block copolymers PEG block copolymer micelles/nanoparticles Covalently grafted PEG Block copolymer adsorbed Block copolymer entangled Carrier surface e.g. Pluronics: PEO PPO PEGylated carriers: protein PEG chain (Shi et al. 2002) liposomes Potential for membrane fusion ƒ PEG binds 2-3 water molecules per repeat unit5 o Causes PEGylated compounds to function as though they are 5-10 times larger than their true molar mass ƒ Observed in SEC and gel electrophoresis experiments4 ƒ PEG/water ‘shield’ can reduce activity of protein, but generally the increased circulation time makes up for this Theory of stealth particle repulsion of protein binding to carriers6,7 o Theory of Halperin7 , building on previous analyses of Alexander/de Gennes and Szleifer