Poly(amino acid)s: promising enzymatically degradable stealth coatings for liposomes.
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.
Romberg
Birgit
B
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. B.Romberg@pharm.uu.nl
Metselaar
Josbert M
JM
Baranyi
Lajos
L
Snel
Cor J
CJ
Bünger
Rolf
R
Hennink
Wim E
WE
Szebeni
Janos
J
Storm
Gert
G
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
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D008081:Liposomes; D009757:Nylons; D010447:Peptide Hydrolases