【作者】 吕雪丽； 刘媛； 祝瑶露； 赵博欣； 魏理； 李国锋；

【Author】 LV Xueli;LIU Yuan;ZHU Yaolu;ZHAO Boxin;WEI Li;LI Guofeng;Department of Pharmacy,The First Affiliated Hospital of Guangzhou Medical University;Department of Pharmacy,NanFang Hospital,Southern Medical University;Rational Medication Evaluation and Drug Delivery Technology Lab,NanFang Hospital,Southern Medical University;Guangdong Key Laboratory of New Drug Screening,School of Pharmacy,Southern Medical University;

【机构】 广州医科大学附属第一医院药学部； 南方医科大学南方医院药学部； 南方医科大学南方医院合理用药评价与药物递送发展实验室； 南方医科大学药学院广东省新药筛选重点实验室；

【摘要】 目的以中药组份甘草酸为载体,按照阿霉素与甘草酸的不同比例制备阿霉素-甘草酸分子复合物（ADR-GL复合物）,探究其在p H=7.4下的溶解度差异并初步评价其抗肿瘤效果。方法按照阿霉素与甘草酸摩尔比2:1,1:1,1:2的量（ADR:GL=2:1,1:1,1:2）投料,采用旋蒸法制备ADR-GL分子复合物并经红外光谱（FT-IR）和差式扫描量热（DSC）分析鉴定所得固体复合物。将ADR-GL复合物溶解于pH=7.4的磷酸盐缓冲液中,过夜超声后3000r/min离心5min得ADR-GL复合物饱和溶液,采用高效液相色谱法测定其中的阿霉素溶解度。最后,MTT法测定ADR-GL对肝癌细胞Hep G2的增殖抑制作用,及经流式细胞仪测定CD44+MDA-MB-231干细胞所占总MDA-MB-231细胞的比例以初步探究其抗肿瘤活性。结果 ADR-GL复合物中阿霉素1525cm^-1红外光谱吸收峰消失,且DSC分析显示ADR-GL在86℃处出现一个明显的新的吸收峰,表明阿霉素可能被甘草酸所包裹而以新的形式存在,称之为"ADR-GL分子复合物"。对照组盐酸阿霉素组在pH=7.4的磷酸盐缓冲液中溶解度为0.844±0.011mmol/L,ADR-GL复合物组与对照组相比溶解度均有显著性差异（P<0.05）,其中阿霉素与甘草酸摩尔比为1:2组溶解度最高,为5.562±0.049mmol/L,是对照组的6.3倍。此外,与阿霉素对照组相比,ADR-GL分子复合物组对Hep G2细胞活力的直接影响及对MDA-MB-231肿瘤干细胞群比负作用二者无显著差异。结论ADR-GL不降低阿霉素抗肿瘤活性,其可能是一种潜在的安全的具有开发价值的新颖递药系统。更多还原

【Abstract】 Objective To prepare an adriamycin-glycyrrhizin molecular complex(ADR-GL complex) using glycyrrhizin(GL,a component in traditional Chinese drug) as the carrier and assess the solubility and anti-tumor activity of the complex.Methods Dried solid products of ADR-GL complex with different molar ratios of ADR and GL(2∶1,1∶1,and 1∶2) were prepared by rotary steaming and characterized using FT-IR and DSC.The products were dissolved in pH7.4 phosphate buffer,sonicated overnight,and centrifuged to obtain saturated ADR-GL complex solution,and ADR solubility was determined using high-performance liquid chromatography(HPLC).The cytotoxicity of ADR and ADR-GL complex was evaluated in HepG2 cells by assessing the cell viability using MTT assay.Breast cancer MDA-MB-231 cells were treated with ADR-GL complex and the proportion of CD44 + cells in the total cells was measured by flow cytometry to evaluate the antitumor activity of the complex.Results FT-IR spectrum of solid ADR-GL complex did not show the absorption peak of adriamycin at 1525 cm-1,and an intense absorption peak of ADR-GL occurred at 86 ℃in DSC,indicating that ADR molecules were encapsulated by GL in a new form of ADR-GL molecular complex.The solubility of ADR in pH7.4 phosphate buffer in the control group was 0.844±0.011 mmol/L,significantly different from that in ADR-GL complex group(P<0.05).The ADR-GL complex with an ADR to GL ratio of 1∶2 showed the highest ADR solubility(5.562±0.049 mmol/L),which was 6.3 times that of the control sample.The ADR-GL complex and ADR showed similar inhibitory effects on HepG2 cells and the negative stemness population of MDA-MB-231 stem cells.Conclusion The ADR-GL complex does not reduce the antitumor activity of ADR and may serve potentially as a safe and novel drug delivery system.更多还原