Steric stabilization of liposomes by pH-responsive N-isopropylacrylamide copolymer.
The aim of this study was to characterize a pH-sensitive liposome formulation bearing a terminally alkylated N-isopropylacrylamide (NIPAM) copolymer with regard to its pH responsiveness, surface properties, and pharmacokinetics. The interacting forces between two lipid bilayers bearing the anchored NIPAM copolymer were measured with a surface force apparatus. The pH-triggered content release was evaluated in buffer before and after incubation in human serum. The pharmacokinetics was determined in rats following the intravenous injection of 67Ga-loaded liposomes with or without the polymer coating. The force measurements between lipid bilayers showed that NIPAM copolymers provide a steric barrier that was dependent on pH. The pH-sensitive liposomes maintained their pH sensitivity after incubation in serum. In vivo, the polymer-coated liposomes exhibited a prolonged circulation time in rats, with an area under the blood concentration-time curve that is 1.6-fold higher than the control formulation. This study showed that liposomes can be rendered pH sensitive by anchoring a terminally alkylated NIPAM copolymer at their surface. At neutral pH, the polymer provides a steric barrier that increases the liposome circulation time in vivo.
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, Université de Montréal, C.P. 6128 Succ. Centre-ville, Québec, Canada H3C 3J7.
Emmanuelle
E
Roux
Romain
R
Stomp
Suzanne
S
Giasson
Michel
M
Pézolet
Pierre
P
Moreau
Jean-Christophe
JC
Leroux
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry*; D000465:Algorithms; D000478:Alkylation; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008051:Lipid Bilayers; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
D000178:Acrylamides; D008051:Lipid Bilayers; D008081:Liposomes; C067295:N-isopropylacrylamide