Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (22): 3536-3541.doi: 10.3969/j.issn.2095-4344.1280

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Preparation, sustained release and anti-tumor characteristics of hydroxypropyl chitosan/heparin nano-drug system

Du Jianhong1, Fan Chunshui1, Du Yuelian1, Sun Xiaoyu1, Wang Qingfeng2
  

  1. 1Department of Pharmaceutical Engineering, ShanXi Pharmaceutical College, Taiyuan 030031, Shanxi Province, China; 2Basic Medical School of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
  • Contact: Du Jianhong, Department of Pharmaceutical Engineering, ShanXi Pharmaceutical College, Taiyuan 030031, Shanxi Province, China
  • About author:Du Jianhong, Master, Lectuner, Department of Pharmaceutical Engineering, ShanXi Pharmaceutical College, Taiyuan 030031, Shanxi Province, China

Abstract:

BACKGROUND: When heparin drugs are used in human body, there are some clinical problems such as high toxicity and short-term metabolism.
OBJECTIVE: To prepare hydroxypropyl chitosan/heparin nano-drug system, and to investigate its drug loading, micromorphology, particle size distribution, in vitro release and inhibitory effect on hepatocellular carcinoma cells.
METHODS: The volume ratios of heparin solution and hydroxypropyl chitosan solution were set as 3:10, 6:10 and 9:10, and the hydroxypropyl chitosan/heparin nanoparticles were prepared by charge attraction method and to detect its property. The 24-hour release rate of the particle in PBS with pH=2.1, 4.6 and 7.4 was investigated. The SMMC-7721 cell lines were inoculated in 96-well plate. Meanwhile, heparin (2.5, 5, 10, and 20 mg/L), and hydroxypropyl chitosan/heparin nanoparticles were added. After cultured for 24 hours, the cell inhibition rate was measured.
RESULTS AND CONCLUSION: (1) When the volume ratio of heparin solution and hydroxypropyl chitosan was 3:10, 6:10 and 9:10, the corresponding drug loads were (27.13±0.79)%, (36.39±1.12)% and (43.68±1.45)%, respectively. (2) The release rate for heparin of the nanoparticles prepared by the volume ratio of heparin solution and hydroxypropyl chitosan of 6:10 under the condition of pH=7.4 was faster than that under the condition of pH=2.1 or 4.6, which could release more than 95% heparin at 6 hours. At the same time, the release rate was proportional to the heparin load. (3) Hydroxypropyl chitosan solution showed no significant inhibition on the SMMC-7721 cell lines. With the increase of solution concentration, the inhibition of heparin on the SMMC-7721 cell lines increased significantly. In addition, the inhibitory effect of hydroxypropyl chitosan/heparin granules prepared when the volume ratio of heparin solution and hydroxypropyl chitosan was 6:10 was better than that of heparin alone. (4) These results indicate that the hydroxypropyl chitosan/heparin nano-loaded drug system with the 6:10 volume ratio of heparin solution and hydroxypropyl chitosan can achieve sustained release of pH sensitivity, and exerts significant inhibition on the tumor.

Key words: drug load, nanoparticles, pH sensitivity, hydroxypropyl chitosan, heparin, SMMC-7721, clonogenesis, liver cancer, sustained-release characteristics

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