响应面法优化制备蓝萼甲磺丁醚-β-环糊精包合物及体外活性研究

Optimization of preparation and in vitro bioactivity study of blue calyx mesylate-β-cyclodextrin inclusion complex by response surface methodology

目的采用包合物的制剂手段,改善蓝萼甲素A(GLA)水溶性,同时提高GLA抑制癌细胞增值的效果。方法采用超声波法将GLA包封在磺丁基醚β-环糊精(SBE-β-CD)中形成包合物(GLA-SBE-β-CD),采用Box-Behnken设计优化GLA-SBE-β-CD包合物的制备工艺,并且通过差示扫描量热法(DSC)、X射线衍射(XRD)和扫描电子显微镜(SEM)对制备的包合物进行表征。最后,使用MTT法检测GLA和GLA-SBE-β-CD包合物对人宫颈癌细胞Hela、人肺癌细胞A549、人肝癌细胞HepG2和人宫颈鳞癌细胞SiHA的抑制作用。结果一系列物理表征结果证实了GLA-SBE-β-CD包合物被成功制备,在Box-Behnken优化的基础上获得87.28%的包合率;确定了SBE-β-CD浓度为18.5%,包合温度为35℃,包合时间为42 min。在最佳工艺条件下进行制备,平均产率为87.28%,相对标准偏差(RSD)为1.02%;同时人源癌细胞抑制实验中GLA-SBE-β-CD对Hela、A549、HepG2和SiHA这4种肿瘤细胞的抑制率比纯GLA更高。结论通过超声波法可成功制备GLA-SBE-β-CD包合物,该包合物在抑制肿瘤细胞生长方面明显高于原料药GLA,说明通过制剂手段能够很好地提高原料药的药效作用,为能早日帮助患者摆脱病痛带来有价值的参考和制剂依据。

Objective To improve the poor water solubility of glaucocalysin A(GLA)and enhance the inhibitory effect of GLA on the proliferation of cancer cells by means of inclusion compound.Methods GLA was encapsulated in sulfobutyl ether by ultrasonic method.β-Cyclodextrin(sulfobutyl ether)β-Cyclodextrin,SBE-β-Forming inclusion complex(GLA-SBE)in CD-β-GLA-SBE was optimized by Box-Behnken design.The inclusion complex was characterized by differential scanning calorimetry(DSC),X-ray diffraction(XRD)and scanning electron microscopy(SEM).Finally,GLA and GLA-SBE-β-CD were detected by MTT method.The inhibitory effect of CD inclusion complex on HeLa,A549,HepG2 and SiHa human cancer cells was studied.Results A series of physical characterization results confirmed GLA-SBE-β-CD on the basis of Box-Behnken optimization.The inclusion rate was 87.28%.The concentration of GLA-SBE-β-CD was 18.5%.The inclusion temperature was 35℃,and the inclusion time was 42 min.The aver-age yield was 87.28%,and the relative standard deviation(RSD)was 1.02%.At the same time,GLA-SBE-β-CD was detected in the inhibition test of human cancer cells.The inhibition rate of GLA-SBE-β-CD on these four kinds of tumor cells was higher than that of pure GLA.Conclusion GLA-SBE-β-CD is successfully prepared by ultrasonic method.The inclusion complex of GLA-SBE-β-CD can significantly inhibit the growth of cancer cells,which is higher than that of GLA,which does not form the inclusion complex.It shows that the drug efficacy of the drug can be improved by means of preparation,which can provide valuable reference and preparation basis for helping patients get rid of pain as soon as possible.