Release property of temperature-sensitive liposome containing poly( N-isopropylacrylamide)

Abstract

Multilamellar vesicles(MLVs) of Egg phosphatidylcholine (PC) were prepared by either reverse-phase evaporation or film hydration method, and dioleoylphosphatidylethanolamine (DOPE) liposomes by detergent removal. Their temperature-dependent release behaviours were investigated in the presence of copolymer of N-isopropylacrylamide and octadecylamine (poly(NIPAM-co-ODA)) or copolymer of N-isopropylacrylamide, acrylic acid and octadecylamine (poly(NIPAM-co-AA-co-ODA)) using calcein a fluorescence probe. By a temperature jump from 17 to 40 °C, crossing the transition temperature of poly(NIPAM-co-ODA), ∼29 °C, the release from reverse-phase evaporation vesicles (REVs) containing the polymer in 270 s increased in a saturation manner until the mixing ratio of polymer to lipid was 0.1, where the degree of release was ∼55%. For the film hydration vesicles (FHVs), the release pattern with polymer to lipid ratio was similar to that of REVs, but the degree of release under the same conditions was much less than in case of REVs, even though both are composed of the same phospholipid. Since the bilayers of REVs are less in number, and more closely stacked each other than those of FHVs, the defect in the bilayers of REVs would be induced more easily by a thermal contraction of the polymer. For DOPE liposomes, the degrees of releases under the same conditions as in the REVs and the FHVs of egg PC were >80%. The extensive release is probably because that the DOPE liposomes disintegrated into nonbilayer structure. On the other hand, in the temperature-dependent release from liposomes mixed with either poly(NIPAM-co-ODA) or poly(NIPAM-co-AA-co-ODA), of which the transition temperatures are ∼29 and 37 °C, respectively, REVs and FHVs started to release significantly around the transition temperature of each polymer. However, for DOPE liposomes the temperature where the liposomes start to release is not clear and an appreciable amount of calcein released below the transition temperature. Therefore, REVs and FHVs are expected to be more favorable than DOPE liposomes when the off-on behavior of release at a certain temperature is desired. Of the egg PC liposomes, REVs would be a better choice than FHVs in aspects of degree of release.