Construction of targeted cryptotanshinone liposomes and research on its in vitro anti-glioma effect
10.16438/j.0513-4870.2021-1050
- VernacularTitle:隐丹参酮靶向脂质体的构建及其体外抗脑胶质瘤考察
- Author:
Hua-cong ZHAO
1
,
2
;
Yong-ming WANG
1
,
2
;
Ji-wei CUI
1
,
2
;
Kuan-han FENG
1
,
2
;
Ruo-ning WANG
1
,
2
;
Liu-qing DI
1
,
2
Author Information
1. School of Pharmacy of Nanjing University of Chinese Medicine, Nanjing 210046, China
2. Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
- Publication Type:Research Article
- Keywords:
cryptotanshinone;
peptide;
blood-brain barrier;
liposome;
glioma
- From:
Acta Pharmaceutica Sinica
2021;56(12):3268-3276
- CountryChina
- Language:Chinese
-
Abstract:
Cryptotanshinone (CPT), an active ingredient with the inhibitory effect on brain glioma cells, is trapped with poor solubility and low tumor permeability. Therefore, it is urgent to design nano drug delivery systems characterized with deep penetration and accurate targeting. In the present study, tLyp-1 modified liposomes loaded with CPT (tLipo/CPT) was prepared by emulsion solvent evaporation method. Peptide tLyp-1 which targeting tumor angiogenesis and neuropilin receptors (NRP) was modified on surface of CPT liposomes, with the aim of active targeting brain glioma cells and further release CPT precisely. The size and polymer dispersity index (PDI) of tLipo/CPT were (162.2 ± 14.6) nm and 0.24 ± 0.03. The optimal molar ratio of tLyp-1 modified on CPT liposomes was 0.5% determined by intracellular fluorescence parameters. The morphology displayed a smooth sphericity structure as determined by transmission electron microscope. Efficiency of CPT encapsulated in tLipo/CPT was detected by high performance liquid chromatography. The encapsulation efficiency of CPT was (70.06 ± 7.22) %. Liposomes modified with tLyp-1 peptide (tLipo) were internalized more than liposomes not modified with tLyp-1 (Lipo) by GL261 cells. Fluorescence intensity of tLipo in GL261 cells increased 40% than that of Lipo. Furthermore, we proved that the intake of tLipo/CPT in GL261 cells was mediated by NRP-1 receptor. MTT analysis indicated that tLipo/CPT significantly inhibit the proliferation of GL261 cells. The half maximal inhibitory concentration (IC50) was 5.70 μmol·L-1. In vitro blood-brain barrier (BBB) model experiment indicated that tLipo/CPT could penetration across BBB. Moreover, in vivo fluorescence biodistribution study indicated tail vein injection of DiR labeled tLipo after 0.5 h, DiR fluorescence could be observed in the brain of mice. Even after 24 h, DiR fluorescence still was observed in the brain. Our research certified that tLipo/CPT can penetrate the BBB and show effect of anti-glioma by inhibiting the proliferation of GL261 cells. The animal experiment was carried out in accordance with protocol evaluated and approved by the Ethics Committee of Nanjing University of Chinese Medicine.
