磁性热敏阿霉素脂质体聚集及释药特性的体外观察

Observation of adriamycin assembly and release in vitro using magnetic thermosensitive liposomes

目的:探讨磁场和加热作用下磁性热敏阿霉素脂质体在体外的聚集及释药情况。方法:实验按水浴加热温度分为6组,分别为21、33、39、42和45℃组以及对照组,同时每一组又分为施加磁场组与未施加磁场组2个亚组。利用LY荧光标记阿霉素后,制备成磁性热敏阿霉素脂质体。采用外加磁场定位对磁性热敏阿霉素脂质体进行聚集引导,水浴加热使其释放阿霉素,通过荧光分析仪观察其聚集、释放药物及与腺癌细胞(腺癌细胞株HT-29)结合情况。结果:在体外强磁场作用下磁性热敏阿霉素脂质体出现定向聚集,在水浴加热至33℃时阿霉素开始释放,并可与腺癌细胞结合,42℃时药物释放量可达到90%以上。其中21、33和39℃时释放药物与腺瘤细胞结合率均低于对照组(P<0.01),在39、42和45℃药物释放率施加磁场亚组与未施加磁场亚组比较差异有显著性(P<0.01)。结论:磁场可以明显提高磁性热敏阿霉素脂质体的体外定向聚集性,温度可以控制磁性热敏阿霉素脂质体对阿霉素的释放及其与腺癌细胞的结合。

Objective To study the assembly and release of adriamycin in vitro using magnetic thermosensitive liposomes treated with magnetic field and pyrogenation. Methods All samples were divided into six groups ： 21, 33, 39, 42, 45℃ and control groups according to the temperature of water bath. Lucifer yellow iodoacetamide （LY） was used as a fluorescence marker to adriamycin which was encapsulated by magnetic thermosensitive liposomes. Liposomes was localized under the action of magnetic field, and adriamycin was released through the use of water baths with LY used as a fluorescence marker to observe the assembly and release. Temperature-treated liposomes were mixed with CT-26 cells to measure the binding of the released LY-marked adriamycin to cell surface. Results The magnetic thermosensitive adriamycin liposomes was assembled directionally under magnetic field. The onset of LY release occurred near 33℃, and reached plateau above 42℃ when 90% of the LY was released. The binding with the HT-29 had positive correlation with the release of the LY-marked adriamycin. Conclusion Magnetic field can make the magnetic thermosensitive liposomes drug to assemble directionally, hyperthermia can control the release of drug from magnetic thermosensitive liposomes.