[关键词]
[摘要]
目的 制备大蒜素二烯丙基三硫醚(DATS)微乳(DATS-MEs),评价该微乳载药系统对肿瘤细胞增殖和迁移能力的影响。方法 以HS15为乳化剂,PEG400为助乳化剂,DATS作为油相,水滴定法制备DATS水包油微乳;采用四甲基偶氮唑蓝(MTT)法,评价DATS-MEs对小鼠Lewis肺癌(LLC)细胞及小鼠黑色素瘤B16BL6细胞体外增殖的影响;采用划痕实验评价DATS-MEs对LLC细胞及B16BL6细胞体外水平移行能力的影响。结果 制备的DATS-MEs稳定,外观澄清透明,分散良好;粒径为(16.72±0.22)nm,多分散系数为0.03±0.01,Zeta电位为(-4.98±0.11)mV,DATS在微乳中的包封率为82.89%,载药量为6.28%,在水中的溶解度与裸药组相比增加了约2 367倍。10、30、50 μmol/L的DATS-MEs与大蒜素裸药均能有效抑制LLC细胞和B16BL6细胞的增殖及迁移,并且具有剂量依赖性,其中DATS-MEs的药效强于DATS裸药。结论 将DATS制成微乳,可提高其稳定性,可以有效解决DATS在水中溶解性差的问题,对LLC细胞及小鼠黑色素瘤B16BL6细胞具有较好的增殖抑制能力及迁移抑制能力,具有更好的抗肿瘤增殖及转移的潜力。
[Key word]
[Abstract]
Objective To prepare diallyl trisulfide microemulsion (DATS-MEs) and evaluate its effect on the proliferation and migration of tumor cells. Methods Using HS15 as emulsifier, PEG400 as co-emulsifier and DATS as the oil phase, water titration method was used to prepare DATS-MEs. The influence of DATS-MEs on the proliferation of mouse Lewis cancer LLC cells and mouse melanoma B16BL6 cells in vitro was evaluated by the tetramethyl azoline blue (MTT) methed; Wound healing assay was used to evaluate the effect of DATS-MEs on the migration of LLC and B16BL6 cells in vitro. Results The DATS-MEs obtained was stable, clear, transparent, and well dispersed. The particle size of DATS-MEs was (16.72 ±0.22) nm, the polydispersity index was 0.03 ±0.01 and the Zeta potential was (-4.98 ±0.11) mV. The encapsulation efficiency (EE) of DATS in microemulsion was 82.89%, the drug loading (DL) was 6.28%. The solubility in water increased by about 2 367 fold compared with the free DATS. DATS-MEs and free DATS at concentration of 10, 30, and 50 μmol/L all can effectively inhibit the migration and proliferation of LLC cells and B16BL6 cells in a dose-dependent manner. DATS microemulsion was proved to be more effective than free DATS. Conclusion After assembly into DATS microemulsion, the stability and solubility in water of DATS was enhanced. The anti-proliferation and anti-migration on mouse Lewis LLC cells and mouse melanoma B16BL6 cells were significantly enhanced.
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[基金项目]
江苏省自然科学基金青年基金项目资助(BK20171097);江苏省中医药局科技项目(YB2017033);江苏省科教强卫医学重点人才项目(ZDRCA2016036)