Legumain酶和线粒体双级靶向去氢骆驼蓬碱脂质体的制备及其体外特性评价
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篇名: | Legumain酶和线粒体双级靶向去氢骆驼蓬碱脂质体的制备及其体外特性评价 |
TITLE: | Preparation of Legumain enzyme and mitochondrial double-stage targeted harmine liposome and evaluation of its in vitro characterization |
摘要: | 目的 制备Legumain酶和线粒体双级靶向去氢骆驼蓬碱(HM)脂质体(KA@HM-LPS),并对其制剂学特性、体外抗肿瘤作用及生物相容性进行初步评价。方法首先,筛选KA@HM-LPS的制备方法和均质化方法,并对制备的脂质体进行表征。其次,分别测定KA@HM-LPS的血清稳定性、体外释放率、溶血百分数,以及空白脂质体作用下的细胞存活率。最后,分别测定KA@HM-LPS作用下的细胞存活率、线粒体靶向性和对肝癌细胞迁移和侵袭的抑制作用。结果选择薄膜分散法制备KA@HM-LPS,其包封率为(90.50±0.62)%;选择挤出法作为KA@HM-LPS的均质化方法。所制备的KA@HM-LPS粒径、多分散系数、Zeta电位分别为(211.40±11.67)nm、0.316±0.014和(-14.20±0.49)mV。在37℃、10%胎牛血清中,12h后KA@HM-LPS的粒径基本稳定;KA@HM-LPS在20%血浆中的体外释放曲线符合Weibull分布,具有缓释效果;当HM质量浓度为160μg/mL时,KA@HM-LPS的溶血百分数为(4.23±0.19)%,远小于游离HM,具有安全性。当空白脂质体的质量浓度达400μg/mL时,LO2细胞的存活率为(94.40±6.12)%,载体生物相容性较好。体外细胞实验结果显示,KA@HM-LPS对Legumain酶过表达的肝癌细胞LGMN+-SK-Hep-1的抑制作用显著高于对正常肝癌细胞SK-Hep-1的抑制作用;且与SK-Hep-1细胞相比,LGMN+-SK-Hep-1细胞对载体的摄取效率更高;KA@HM-LPS可以更明显地抑制LGMN+-SK-Hep-1细胞的迁移和侵袭。结论成功制备KA@HM-LPS;该脂质体可以有效抑制Legumain酶过表达的肝癌细胞的迁移和侵袭,并提高HM的血液相容性。 |
ABSTRACT: | OBJECTIVE To prep are Legumain enzyme and mitochondrial double-stage targeted harmine (HM) liposome (KA@HM-LPS)and preliminary evaluate its pharmaceutical properties ,in vitro antitumor effect and biocompatibility. METHODS Firstly,the preparation and homogenization methods of KA@HM-LPS was screened ,and prepared liposomes were characterized. Secondly,the serum stability ,in vitro release rate ,hemolysis percentage of KA@HM-LPS and cell survival rate under KA@BLPS were determines respectively. Finally ,the cell surivival rate ,mitochondrial targeting and inhibitory effects on cell migration and invasion of KA@HM-LPS were determined. RESULTS KA@HM-LPS was prepared by the thin-film dispersion method ,with encapsulation efficiency of (90.50 ± 0.62)% . The extrusion moulding method was selected as homogenization method of KA@HM-LPS. The particle size ,polydispersity index ,and Zeta potential of KA@HM-LPS were (211.40±11.67)nm,0.316± 0.014 and(-14.20±0.49)mV,respectively. In 37 ℃,10% FBS,the particle size of KA@HM-LPS kept stable after 12 h. In vitro release curve of KA@HM-LPS in 20% plasma conformed to Weibull distribution and had the property of sustained release. When HM concentration was 160 μg/mL,the hemolysis percentage of KA@HM-LPS was (4.23±0.19)%,which was much lower than that of free HM ,with safety. When the mass concentration of KA@BLPS reaches 400 μg/mL,the survival rate of LO 2 cells was (94.40 ± 6.12)% ,and the biocompatibility was good. Cell test results in vitro showed that ,inhibitory effect of KA@HM-LPS on liver cancer cells with overexpression of Legumain enzyme (LGMN -SK-Hep-1) was significantly higher than that of normal liver cancer cells SK-Hep- 1; compared with SK-Hep-1,LGMN +-SK-Hep-1 cells had a higher uptake efficiency of the liposome ;KA@HM-LPS could significantly inhibit the migration and invasion of LGMN +- SK-Hep-1 cells. CONCLUSIONS KA@HM-LPS is prepared successfully ,which can effectively inhibit the migration and invasion of liver cancer cells with Legumain enzyme overexpression ,and improve the blood compatibility of HM. |
期刊: | 2022年第33卷第13期 |
作者: | 伊帕尔古丽·阿皮孜,贺宏吉,王昭志,李喆喆,卡迪热娅·艾克拉木,白静雅,王梅 |
AUTHORS: | Ipargul·Hafiz,HE Hongji ,WANG Zhaozhi ,LI Zhezhe ,Kadirya·Akram,BAI Jingya ,WANG Mei |
关键字: | 去氢骆驼蓬碱;线粒体;Legumain酶;脂质体 |
KEYWORDS: | harmine;mitochondria;Legumain enzyme ;liposome |
阅读数: | 149 次 |
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