Thermosensitive polymer-modified liposomes that release contents around physiological temperature

To obtain temperature-sensitive liposomes which release their contents around the physiological temperature, we designed dioleoylphosphatidylethanolamine liposomes modified with copolymers of N-isopropylacrylamide and acryloylpyrrolidine. Copolymers of acryloylpyrrolidine and N-isopropylacrylamide, which exhibit a lower critical solution temperature around the physiological temperature, were prepared by free radical copolymerization using azobis(isobutyronitrile) as the initiator. The copolymers with anchors to the liposome membrane were obtained by using N, N-didodecylacrylamide as an additional comonomer. The copolymer having the anchor group at the terminal of the polymer chain was also synthesized by copolymerization of these monomers in the presence of 2-aminoethanethiol and subsequent conjugation of N,N-didodecyl succinamic acid to the terminal amino group of the copolymer. Calcein-loaded dioleoylphosyhatidylethanolamine liposomes modified with these copolymers were prepared and release of the contents from these liposomes was investigated. It was found that the release from these copolymer-modified liposomes was promoted around and above the lower critical temperature of the copolymer. Also, the liposomes modified with the terminal anchor-type copolymer released the contents more drastically responding to a small temperature change than the liposomes modified with random copolymers containing N, N-didodecylacrylamide units as the anchor. (C) 1999 Elsevier Science B.V. All rights reserved.