Preparation of Legumain enzyme and mitochondrial double-stage targeted harmine liposome and evaluation of its in vitro characterization
- VernacularTitle: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
- Author:
Hafiz IPARGUL
1
;
Hongji HE
1
;
Zhaozhi WANG
1
;
Zhezhe LI
1
;
Akram KADIRYA
1
;
Jingya BAI
1
;
Mei WANG
1
Author Information
1. College of Pharmacy,Xinjiang Medical Univer sity,Urumqi 830017,China
- Publication Type:Journal Article
- Keywords:
harmine;
mitochondria;
Legumain enzyme;
liposome
- From:
China Pharmacy
2022;33(13):1565-1572
- CountryChina
- Language:Chinese
-
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.