Temperature-controlled release property of phospholipid vesicles bearing a thermo-sensitive polymer.

As a novel temperature-sensitive liposome, dioleoylphosphatidylethanolamine vesicles bearing poly(N-isopropylacrylamide), which shows a lower critical solution temperature (LCST) near 32 degrees C, were designed. Poly(N-isopropylacrylamide) having long alkyl chains which are anchors to the lipid membranes was prepared by radical copolymerization of N-isopropylacrylamide and octadecyl acrylate using azobisisobutyronitrile as the initiator. The copolymer obtained revealed the LCST at about 30 degrees C in an aqueous solution. Dioleoylphosphatidylethanolamine vesicles coated with the copolymer was prepared and release property of the copolymer-coated vesicles was investigated. While release of calcein encapsulated in the copolymer-coated vesicles was limited below 30 degrees C, the release was drastically enhanced between 30 and 35 degrees C. Complete release from the vesicles was achieved within several seconds at 40 degrees C. This temperature-controlled release property of the vesicles can be attributable to stabilization and destabilization of the vesicle membranes induced by the copolymer fixed on the vesicles below and above the LCST, respectively. Moreover, the fluorometric measurement using dioleoyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethan ola mine suggested that the extensive release of calcein observed above the LCST is resulted from the bilayer to HII phase transition of the vesicle membranes. Since LCST of the copolymer is controllable, these vesicles might have potential usefulness as a drug delivery system with high temperature-sensitivity.