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Preparation and in vitro evaluation of macrocyclic metronidazole conjugates as an oral colon-specific delivery system

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Abstract

The antimicrobial drug metronidazole (MTZ) was covalently conjugated to the secondary hydroxyl groups of β-cyclodextrin through ester linkage using sodium hydride as the deproton reagent. The preliminary release behavior of MTZ in rat gastrointestinal tract contents was studied at 37 °C within 24 h. In the contents of stomach, the conjugates did hardly release MTZ, released MTZ only 9.5 % in the contents of small intestine, and released MTZ significantly up to 43.6 and 40.2 % in the contents of cecum and colon, respectively. These results indicate that the conjugate activation took place site-specifically in the rat cecal and colonic contents, probably via the biodegradation by glycosidases and hydrolases. The present MTZ-appended cyclodextrin conjugate may be of value as an orally administered delayed-release and/or colon-specific prodrug.

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Acknowledgments

All the authors are grateful to Ningxia Medical University, for providing laboratory facilities. Financial support from the Ningxia’s Natural Science Foundation (No. NZ12178) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pharmacy, General Hospital, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China

    Zhizhong Wang, Benpeng Li, Peipei Ma, Wencheng Yang, Mengying Liu, Qing Huang & Shijie Wei

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  1. Zhizhong Wang
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  2. Benpeng Li
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  3. Peipei Ma
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  4. Wencheng Yang
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  5. Mengying Liu
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  6. Qing Huang
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  7. Shijie Wei
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Correspondence to Shijie Wei.

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Wang, Z., Li, B., Ma, P. et al. Preparation and in vitro evaluation of macrocyclic metronidazole conjugates as an oral colon-specific delivery system. J Incl Phenom Macrocycl Chem 78, 501–504 (2014). https://doi.org/10.1007/s10847-013-0339-5

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