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A Cremophor-Free Self-Microemulsified Delivery System for Intravenous Injection of Teniposide: Evaluation In Vitro and In Vivo

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Abstract

In order to tackle the problems on low water solubility of teniposide, involvement of toxic surfactant in its injection, and the poor stability during infusion, a Cremophor-free teniposide self-microemulsified drug delivery system (TEN-SMEDDS) was prepared for the first time, characterized, and evaluated in comparison with teniposide injection (VUMON) in vitro and in vivo. The optimized formulation contained N, N-dimethylacetamide, medium-chain triglyceride, lecithin, and dehydrated alcohol besides teniposide. The TEN-SMEDDS could form fine droplets with mean diameter of 282 ± 21 nm and zeta potential of −7.5 ± 1.7 mV after dilution with 5% glucose, which were stable within 4 h. The release of teniposide from TEN-SMEDDS and VUMON was similar. However, the pharmacokinetic behavior of TEN-SMEDDS in rats was different from that of VUMON, evidenced by the lower area under the concentration–time curve and larger volume of distribution in emulsion group. Finally, TEN-SMEDDS was found to distribute more teniposide in most tissues, especially in reticuloendothelial system, after intravenous administration to rats. Importantly, brain drug level in TEN-SMEDDS group was higher than or similar to that in control group, although the emulsion system had a lower plasma drug concentration. In conclusion, the novel SMEDDS prepared here, without toxic surfactant and as an oil solution before use, may be potential for clinical use due to its low toxicity and high store stability. It may be favorable for the treatment of some tumors like cerebroma, since it may achieve the relatively higher drug level in brain but lower blood concentration.

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ACKNOWLEDGMENTS

This study was funded by the National Nature Science Foundation (no. 81130059), the National Basic Research Program of China (no. 2009CB930300), and Innovation Team of Ministry of Education (no. BMU20110263). The authors are grateful for the support.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China

    Suna He & Qiang Zhang

  2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China

    Suna He, Zheng Cui, Dong Mei, Hua Zhang, Xueqing Wang, Wenbing Dai & Qiang Zhang

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  1. Suna He
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  2. Zheng Cui
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  3. Dong Mei
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  4. Hua Zhang
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Correspondence to Wenbing Dai.

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He, S., Cui, Z., Mei, D. et al. A Cremophor-Free Self-Microemulsified Delivery System for Intravenous Injection of Teniposide: Evaluation In Vitro and In Vivo . AAPS PharmSciTech 13, 846–852 (2012). https://doi.org/10.1208/s12249-012-9809-0

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