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Preparation and characterization of inclusion complexes of antitumor camptothecin with cucurbit[n = 7, 8]urils

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Abstract

The slightly water-soluble anticancer drug camptothecin (CPT) and its inclusion complexes with cucurbit[n = 7, 8]uril (Q[n] (n = 7, 8)) were investigated. The formation of 1:2 complexes with Q[n] (n = 7, 8) in aqueous solution was confirmed by fluorescence spectroscopy and the apparent stability constants were determined to be higher than 3.01 × 1012 L2/mol2. The solid inclusion complexes of CPT and Q[n] (n = 7, 8) were also prepared by the co-evaporation method and characterized by Fourier transformation-infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Aqueous solubility and dissolution studies indicate that the complexes exhibited significantly increased dissolution rates compared with the pure drug and physical mixtures. The potential of Q[7] or Q[8] for stabilizing lactone modality of CPT was investigated by the High Performance Liquid Chromatography (HPLC) method. The results reveal more than 63% CPT lactone form (active form) in CPT-Q[7] or Q[8] complexes compared to only 36% CPT lactone form in the absence of Q[7] or Q[8] after being incubated in the phosphate buffer solution (pH 7.4 at 37°C) for 5 h.

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Authors and Affiliations

  1. Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang, 550025, China

    Nan Dong, QianJiang Zhu & Zhu Tao

  2. School of Chemistry and Chemical Engineering, Guizhou University, Guiyang, 550025, China

    MeiYu Dong & AnTing Zhao

  3. Institute of Material Medical, College of Pharmaceutical Science, Zhejiang University, Hangzhou, 310058, China

    Yu Zhao

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  1. Nan Dong
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  2. MeiYu Dong
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  3. AnTing Zhao
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  4. QianJiang Zhu
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  5. Zhu Tao
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  6. Yu Zhao
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Correspondence to Nan Dong or QianJiang Zhu.

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Dong, N., Dong, M., Zhao, A. et al. Preparation and characterization of inclusion complexes of antitumor camptothecin with cucurbit[n = 7, 8]urils. Sci. China Chem. 53, 2304–2310 (2010). https://doi.org/10.1007/s11426-010-4067-z

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  • DOI: https://doi.org/10.1007/s11426-010-4067-z

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