TEMPERATURE-DEPENDENT ASSOCIATING PROPERTY OF LIPOSOMES MODIFIED WITHA THERMOSENSITIVE POLYMER

Novel temperature-sensitive liposomes having surface properties that c an be controlled by temperature were designed as liposomes coated with poly(N-isopropylacrylamide), which exhibits a hydrated coil to dehydr ated globule transition at ca. 32 degrees C. To obtain the polymer wit h anchoring groups to the liposome, a copolymer of N-isopropylacrylami de and octadecyl acrylate (99:1, mol/mol) was synthesized by radical c opolymerization. The copolymer revealed the transition near 30 degrees C. Liposomes made from various phospholipids were prepared by sonicat ion and coated with the copolymer. When dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine were used as liposome lipids, remar kable aggregation and fusion of the copolymer-modified liposomes took place between the transition temperature of the copolymer and the gel- liquid-crystalline transition temperature (T-c) of the lipid membranes . However, above the T-c, association between the liposomes was much l ess significant, although the copolymer is still hydrophobic. In the c ase of the copolymer-modified dilauroylphosphatidylcholine liposome, t he membrane of which takes on a liquid-crystalline state under the exp erimental conditions, association between the liposomes also hardly oc curred even when the copolymer became hydrophobic. On the other hand, below the transition temperature of the copolymer, the copolymer-modif ied Liposomes were very stable and aggregation of the liposomes was no t observed, irrespective of membrane Lipid. Results obtained in this s tudy demonstrate that the copolymer chains fixed on the surface of the liposome with a solid membrane promote aggregation and fusion of the liposomes by hydrophobic interactions between the copolymer chains and /or between the copolymer chains and the liposome membranes above the transition temperature of the copolymer.