Development, characterization and anti-tumor effect of a sequential sustained-release preparation containing ricin and cobra venom cytotoxin.
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.
Department of Ultrasonography, Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.
Xiu-Juan
XJ
Zhang
Li-Ming
LM
Ke
Jing
J
Yang
Li-Wu
LW
Lin
En-Sheng
ES
Xue
Yan
Y
Wang
Li-Yun
LY
Yu
Zhi-Kui
ZK
Chen
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004546:Elapid Venoms / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D005079:Excipients; D006801:Humans; D020100:Hydrogels; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009368:Neoplasm Transplantation; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012276:Ricin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D013696:Temperature; D023041:Xenograft Model Antitumor Assays
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004546:Elapid Venoms; D005079:Excipients; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012276:Ricin