title: Polymer vesicles in vivo: correlations with PEG molecular weight.
abstract: PEG-modified lipid vesicles have already shown considerable utility in delaying vesicle clearance from the circulation. They are, however, limited in their ability to stably integrate high molar ratios of PEG-lipid due to the high curvature and micellar preference of the very large hydrophilic PEG chain. Polymersomes, by contrast, are vesicles composed entirely of PEG-based block copolymer amphiphiles that are not only more proportionately designed, but also have already been shown to considerably broaden the range of vesicle properties (e.g. stability). Here, polymersomes composed of varying length copolymer chains were injected into rats and found to have in vivo circulation times, tau(1/2), up to about two-fold longer than PEGylated, or Stealth, liposomes. The dependence of tau(1/2) on PEG molecular weight is nonetheless limited by uptake into the liver and spleen-as with liposomes. In vitro incubations of polymersomes in plasma indicate gradual opsonization through plasma protein adsorption, such that, when vesicles are held in an optical trap and presented to a phagocyte, rapid engulfment occurs only after incubation times of similar magnitude to tau(1/2). The stealthiness introduced to liposomes through PEGylation is thus extended here with completely synthetic polymersomes.
authors.affiliation: Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104-6393, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Photos
authors.forename: Lucie
authors.initials: L
authors.lastname: Bacakova
authors.forename: Bohdana
authors.initials: B
authors.lastname: Discher
authors.forename: Frank S
authors.initials: FS
authors.lastname: Bates
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Discher
mesh_terms: D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D011092:Polyethylene Glycols