Cremophor-free intravenous self-microemulsions for teniposide: Safety, antitumor activity in vitro and in vivo

详细信息    查看全文

• 作者：Suna He^a ; ^b ; Zheng Cui^a ; Xueqing Wang^a ; Hua Zhang^a ; Wenbing Dai^a ; Qiang Zhang^a ; ^{zqdodo@bjmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Teniposide self-microemulsified drug delivery system ; Hemolysis ; Hypersensitivity ; Vein irritation ; Toxicity in vivo ; Antitumor activity
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：10 November 2015
• 年：2015
• 卷：495
• 期：1
• 页码：144-153
• 全文大小：2165 K

文摘

The study was designed to identify the safety and antitumor activity of teniposide self-microemulsified drug delivery system (TEN-SMEDDS) previously developed, and to provide evidence for the feasibility and effectiveness of TEN-SMEDDS for application in clinic. The TEN-SMEDDS could form fine emulsion with mean diameter of 279 ± 19 nm, Zeta potential of −6.9 ± 1.4 mV, drug loading of 0.04 ± 0.001% and entrapment efficiency of 98.7 ± 1.6% after dilution with 5% glucose, respectively. The safety, including hemolysis, hypersensitivity, vein irritation and toxicity in vivo, and antitumor activity were assessed, VUNON as a reference. Sulforhodamine B assays demonstrated that the IC50 of TEN-SMEDDS against C6 and U87MG cells were higher than that of VUMON. But the effect of TEN-SMEDDS on the cell cycle distribution and cell apoptotic rate was similar to that of VUMON as observed by flow cytometry. Likewise, the antitumor activity of TEN-SMEDDS was considerable to that of VUMON. Finally, the TEN-SMEDDS exhibited less body weight loss, lower hemolysis and lower myelosuppression as compared with VUMON. In conclusion, promising TEN-SMEDDS retained the antitumor activity of teniposide and was less likely to cause some side effects compared to VUMON. It may be favorable for the application in clinic.