title: Poly(amino acid)s: promising enzymatically degradable stealth coatings for liposomes.
abstract: Poly(amino acid)s (PAAs) were evaluated as coating polymers for long-circulating liposomes. The pharmacokinetics of PAA-coated liposomes were assessed in rats. Prolonged circulation times were obtained, comparable to those reported for poly(ethylene glycol) (PEG)-liposomes. Besides, the enzymatic degradability of PAAs was studied. PAAs - in free as well as liposome-associated form - are degradable by proteases, which is beneficial for reducing the risks of accumulation in vivo. Furthermore, complement activation by PAA-liposomes was evaluated in vitro and in vivo. Like other liposome types, they appear to activate the complement system. However, a role of endotoxin contamination of the PAA-liposome formulations used cannot be excluded in our complement activation studies.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. B.Romberg@pharm.uu.nl
authors.forename: Birgit
authors.initials: B
authors.lastname: Romberg
authors.forename: Josbert M
authors.initials: JM
authors.lastname: Metselaar
authors.forename: Lajos
authors.initials: L
authors.lastname: Baranyi
authors.forename: Cor J
authors.initials: CJ
authors.lastname: Snel
authors.forename: Rolf
authors.initials: R
authors.lastname: Bünger
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Janos
authors.initials: J
authors.lastname: Szebeni
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D003167:Complement Activation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D009757:Nylons / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D010447:Peptide Hydrolases / Q000378:metabolism; D010599:Pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D008081:Liposomes; D009757:Nylons; D010447:Peptide Hydrolases