包覆NIPAM-ODA双亲共聚物的脂质体的温控释放行为

TEMPERATURECONTROLLED RELEASE OF AN AQUEOUS MARKER FROM LIPOSOMES COATED WITHNIPAMODA COPOLYMERS

为了研究对温度敏感的双亲性共聚物包覆的脂质体的温控释放行为，合成了Ｎ异丙基丙烯酰胺（ＮＩＰＡＭ）和丙烯酸十八酯（ＯＤＡ）的共聚物．利用荧光探针法研究了共聚物水溶液随温度升高时出现的ＬＣＳＴ（ｌｏｗｅｒｃｒｉｔｉｃａｌｓｏｌｕｔｉｏｎｔｅｍｐｅｒａｔｕｒｅ）现象，表明该高分子在温度升高到３０℃以上时存在着明显的相分离行为．以５（６）羧基荧光素（５（６）ＣＦ）为标记物，研究了高分子包覆的小单层脂质体（ｓｍａｌｕｎｉｌａｍｅｌａｒｖｅｓｉｃｌｅｓ）的释放行为．发现在温度低于３０℃时，５（６）ＣＦ的释放百分率比未包覆高分子的脂质体要低；而当温度升高到３０℃以上时，其释放百分率明显提高．这种温控释放行为和包覆在脂质体上的高分子在其ＬＣＳＴ时存在的相分离行为有关．进一步利用荧光偏振法研究了脂质体膜在包覆高分子后的流动性变化，发现：在温度低于３０℃时，其流动性随温度升高而增大；而在温度高于３０℃时，脂质体膜流动性随温度升高而降低。

To study the temperaturecontrolled release behavior of the liposome coated with an amphiphilic copolymer which is temperaturesensitive, the copolymer of Nisopropylacrylamide (NIPAM) and octadecyl acrylate (ODA) was synthesized. The phenomenon of LCST(Lower Critical Solution Temperature)of the copolymer in aqueous solution with the increase of the temperature was studied by using fluorescence probe method. Results showed that the obvious phase separation occurs when temperature was increased to 30 . The release property of small unilamellar vesicles (SUV) coated with the copolymer was studied by using 5(6)carboxyfluorescein (5(6)CF) as a water soluble marker. Results showed that the coating of the copolymer on the liposomal surface resulted in reduction of the release below 30 and enhancement of the release above 30 . It indicated that the temperaturecontrolled release behavior of the liposome was directly related to the phase separation behavior of the coating copolymer when temperature was increased to its LSCT. Moreover, fluorescence polarization method was used to study the influence of the coating copolymer on the fluidity of the liposomal membrane. Results showed that at temperature below 30 the fluidity of the liposomal membrane increased with the increase of temperature; however, at temperature above 30 the fluidity of the liposomal membrane decreased with the increase of temperature. It further indicated that the copolymer which was bound at the surface of the liposome can destroy the liposomal membrane when temperature was increased at or above its LCST.