Development, characterization and anti-tumor effect of a sequential sustained-release preparation containing ricin and Cobra venom cytotoxin

作者：Xiujuan Zhang, Li-ming Ke, Jing Yang, Liwu Lin, Ensheng Xue, Yan Wang, Liyun Yu, Zhikui Chen · 发表于：Die Pharmazie · 年份：2012 · DOI：10.31083/ph.2012.1787 · 被引用次数：7 · 研究领域：Toxin Mechanisms and Immunotoxins、Monoclonal and Polyclonal Antibodies Research、Bioactive Compounds and Antitumor Agents

Cobra venom cytotoxin (CVC) loaded in poly (lactide-co-glycolide) (PLGA) microspheres was mixed with ricin and encapsulated in a thermosensitive PLGA-PEG-PLGA hydrogel for this study. This sequential sustained-release preparation (SSRP) containing ricin and CVC could avoid burst release effect of CVC from microspheres. In addition, in SSRP, the two biotoxins have different drug release rates and antitumor mechanisms, which can be complementary to each other. Ricin has a faster release rate than CVC. It can combine with the tumor cell membrane and enter the cell, inhibiting protein synthesis within 2 weeks. Whereas CVC releases slowly in 5 weeks directly dissolving the tumor cell membrane and killing the cells which are less-sensitive to ricin. The in vivo experiments showed that intratumoral injection of SSRP could inhibit hepatocellular carcinoma growth significantly, and the tumor growth inhibition rate reached 73.5%. It appears that a new medicine preparation for cancer local treatment should be further studied for clinical applications.