Development of Triptolide Self-Microemulsifying Drug Delivery System and Its Anti-tumor Effect on Gastric Cancer Xenografts

• Main Authors: Minghua Xie, Jia Wu, Liqaing Ji, Xiaorui Jiang, Jin Zhang, Min Ge, Xinjun Cai
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-10-01
• Series: Frontiers in Oncology
• Subjects: triptolide; self-microemulsifying delivery system; central composite design and response surface methodology; MGC80-3 cells; anti-tumor effect
• Online Access: https://www.frontiersin.org/article/10.3389/fonc.2019.00978/full

Purpose: To develop a triptolide (TP) self-microemulsifying drug delivery system and to investigate its anti-tumor effect on human gastric cancer line MGC80-3 xenografts in nude mice.Methods: The medium chain triglyceride (MCT) was selected as oil phase; polyoxyethylene castor oil (EL) was selected as surfactant, and PEG-400 was selected as cosurfactant. The mass ratio of each phase was optimized by central composite design and response surface methodology to prepare TP-SMEDDS (self-microemulsifying drug delivery system). The quality of TP-SMEDDS was evaluated, and its inhibitory effect on tumor growth investigated in nude mice transplanted with MGC80-3 cells.Results: The final prescription process was defined as follows: MCT mass ratio: 25.3%; EL mass ratio: 49.6%; PEG-400 mass ratio: 25.1%. The prepared TP-SMEDDS was a transparent liquid with a clear appearance (the theoretical particle size: 31.168 nm). On transmission electron microscopy, the microemulsion particles were spherical in size and uniformly distributed without adhesions. The in vitro release experiment showed complete release of the prepared TP-SMEDDS in PBS solution in 6 h. In vivo antitumor activity showed its inhibitory effect in the xenograft model.Conclusion: The self-microemulsifying delivery system improved the oral bioavailability and the in vivo antitumor effect of TP.