【摘要】：目的制備硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體,并進(jìn)行處方篩選及體外活性研究。方法采用硫酸銨梯度法制備硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體,以包封率及粒徑為評(píng)價(jià)指標(biāo),采用Box-Behnken響應(yīng)面設(shè)計(jì)法優(yōu)化制備工藝,并研究硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)人肝癌SMMC-7721細(xì)胞株的增殖抑制及凋亡的誘導(dǎo)作用。采用CCK-8法檢測(cè)硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)人肝癌SMMC-7721細(xì)胞株的生長抑制情況,采用了Annexin V/PI流式細(xì)胞分析法檢測(cè)細(xì)胞凋亡。結(jié)果最佳工藝:藥與磷脂比為1∶14.95,膽固醇與磷脂之比為1∶4.45,水浴溫度為61.93℃,硫酸銨溶液的體積為4.31 m L。硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體的粒徑為(252±6.4)nm,包封率為(68.50±0.85)%。CCK-8細(xì)胞毒性試驗(yàn)結(jié)果顯示,在藥物濃度相同時(shí),抑制率隨時(shí)間的延長而增加;作用時(shí)間相同時(shí),抑制率隨藥物濃度的增大而增加。Annexin V/PI流式試驗(yàn)結(jié)果顯示,硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)人肝癌SMMC-7721細(xì)胞株的抑制率優(yōu)于人肝癌A549細(xì)胞株。結(jié)論硫酸銨梯度法制備硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體的處方合理,工藝可行,包封率高。硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)人肝癌SMMC-7721細(xì)胞株有更高的細(xì)胞毒性,誘導(dǎo)SMMC-7721細(xì)胞株凋亡能力比A549的強(qiáng)。初步判定硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體具有主動(dòng)肝靶向性。
[Abstract]:Objective to prepare stearol galactoside modified acitinib liposomes and to study the prescription screening and in vitro activity of acitinib liposomes. Methods Azetinib liposomes modified by stearyl galactoside were prepared by ammonium sulfate gradient method. The encapsulation efficiency and particle size were used as evaluation indexes. Box-Behnken response surface design was used to optimize the preparation process, and the effect of stearyl galactoside modified acitinib liposomes on proliferation and apoptosis of human hepatocellular carcinoma SMMC-7721 cell line was studied. CCK-8 assay was used to detect the inhibitory effect of stearyl galactoside modified azetinib liposomes on the growth of human hepatocellular carcinoma SMMC-7721 cell line, and Annexin V/PI flow cytometry was used to detect apoptosis. Results the optimum conditions were as follows: the ratio of drug to phospholipid was 1 鈮，

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