Preparation of Small Peptide AEYLR Modified Paclitaxel Nanostructured Lipid Carriers and Evaluation of Its Anti-tumor Effects
- VernacularTitle:AEYLR小肽修饰的紫杉醇纳米结构脂质载体的制备及抗肿瘤效果评价
- Author:
Cuiyan HAN
1
;
Jianwen ZHOU
2
;
Chang LIU
1
;
Xiaoxing MA
1
;
Cheng YUAN
1
;
Yan DONG
1
;
Shanshan JIN
3
Author Information
1. School of Pharmacy,Qiqihar Medical College,Heilongjiang Qiqihar 161006,China
2. School of Pharmacy,Jiamusi University,Heilongjiang Jiamusi 154007,China
3. Dept. of Preparation,Beijing Wanquan Dezhong Pharmaceutical Technolog y Co.,Ltd.,Beijing 102299,China
- Publication Type:Journal Article
- Keywords:
AEYLR;
Small peptide;
Paclitaxel;
Nano- structured lipid carriers;
Anti-tumor;
Mice
- From:
China Pharmacy
2019;30(6):770-775
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: To prepare Paclitaxel(PTX)nanostructured lipid carriers (NLC) modified by small peptide alanine-glutamic acid-tyrosine-leucine-arginine (AEYLR), and to evaluate its anti-tumor effect in vitro and in vivo. METHODS: NLC, PTX-NLC (P-NLC) and AEYLR modified P-NLC (A-P-NLC) were prepared by emulsion evaporation-low temperature solidification curing method. Its appearance, particle size, multi-dispersion index(PDI) and Zeta potential were characterized,encapsulation rate,drug loading and in vitro drug release were detected respectively. Using NCI-H1299 and S180 cells as objects, CCK-8 method was adopted to investigate inhibitory effects of free PTX, P-NLC and A-P-NLC (0.44-44.00 μg/mL, by PTX) to those cells. The half inhibition concentration (IC50) was calculated. Using S180 tumor-bearing mice as model animal, anti-tumor effects of free PTX, P-NLC and A-P-NLC (5 mg/kg, by PTX) were evaluated. RESULTS: P-NLC and A-P-NLC were round-like and dispersed evenly. The particle size, PDI and Zeta potential of A-P-NLC were (43.92±0.76) nm, 0.203±0.034 and (-19.77±1.16) mV, which were all increased to certain extent, compared with P-NLC. The encapsulation efficiency and drug loading of A-P-NLC were (95.71±0.68)% and(1.97±0.25)%, which were both decreased to certain extent, compared with P-NLC. The cumulative release rate of A-P-NLC was(35.17±2.08)% within 48 h, showing significant sustained-release effect compared with free PTX; the release of A-P-NLC was slower than P-NLC. Compared with free PTX and P-NLC, inhibitory rates of same concentration of A-P-NLC to NCI-H1299 cells and S180 cells were almost increased significantly, while IC50 values were all decreased significantly. There was no death in S180 tumor-bearing mice treated with A-P-NLC and the general condition was good; the volume of tumors was significantly reduced, the mass of tumors was significantly reduced, and the inhibition rate of tumors was significantly increased (P<0.05 or P<0.01). CONCLUSIONS: A-P-NLC has significantly sustained-release effects; its inhibitory rate to NCI-H1299 cells and S180 cells in vitro, and its inhibitory effects on S180 solid tumor in mice are all better than free PTX and P-NLC, while the toxicity is decreased to certain extent.