胆固醇衍生物脂质体的物理稳定性和细胞相容性研究

目的：研究胆固醇衍生物（CTBBA）脂质体的物理稳定性,细胞相容性以及药物输送。方法：CTBBA组入脂质体并测定不同pH下的zeta电位。对长期保存的脂质体进行粒径分析和含磷量分析,评价脂质体的物理稳定性。通过测定包封在脂质体内的阿霉素的体外释放,来评价CTBBA对脂质体释放药物的影响。用MTT法检测CTBBA本身以及CTBBA脂质体的细胞相容性。评估了用流式细胞仪和荧光显微镜检测脂质体细胞内药物输送能力的可行性。结果：zeta电位数据表明CTBBA脂质体带有正电荷,可以改善脂质体在长期保存过程中的物理稳定性;作为胆固醇衍生物的CTBBA能有效的降低药物的渗漏;相比某些正电荷载体,CTBBA的细胞毒性较低;流式细胞仪在反映阿霉素脂质体的细胞定位上有局限,固定液的使用会改变阿霉素荧光的细胞内分布。结论：正电荷CTBBA脂质体具有改善脂质体长期保存稳定性,且细胞毒性低的特点。流式细胞仪不能完全反映载药的CTBBA脂质体在细胞内的分布。

Physical Stability and Cytocompatibility of Cholesterol Derivative Combined Liposome

Objective： To investigate physical stability, drug delivery and cytocompatiblity of a cholesterol derivative（CTBBA）combined liposome. Methods： CTBBA was combined with liposome; and zeta potential was analyzed in buffers with different/gradient pH. Size distribution and phosphorus content analysis were carried out to investigate the physical stability of liposome. The effect of CTBBA on drug release profile in vitro was studied. The cytotoxicity of CTBBA or CTBBA-liposome was measured. Finally the intracellular drug delivery was evaluated by flow cytometry analysis and fluorescence microscope. Results： The zeta potential of CTBBA was positive, which improved the physical stability of liposome during the two year storage period. As a cholesterol derivative,CTBBA-liposome could inhibit the drug leakage in vitro. As a positive charged carrier, CTBBA showed a lower cytotoxicity. Flow cytometry analysis could not exactly reveal the intracellular distribution of DOX-liposome, and pretreatment of fixation changed the distribution of DOX-liposome. Conclusion： Positively charged CTBBA-liposome could improve the physical stability with low cytotoxicity. Flow cytometry analysis could not exactly reveal the intracellular distribution of DOX-liposome.