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Improvement in Thermal Stability of Sucralose by γ-Cyclodextrin Metal-Organic Frameworks

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Abstract

Purpose

To explain thermal stability enhancement of an organic compound, sucralose, with cyclodextrin based metal organic frameworks.

Methods

Micron and nanometer sized basic CD-MOFs were successfully synthesized by a modified vapor diffusion method and further neutralized with glacial acetic acid. Sucralose was loaded into CD-MOFs by incubating CD-MOFs with sucralose ethanol solutions. Thermal stabilities of sucralose-loaded basic CD-MOFs and neutralized CD-MOFs were investigated using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and high performance liquid chromatography with evaporative light-scattering detection (HPLC-ELSD).

Results

Scanning electron microscopy (SEM) and powder X-ray diffraction (PXRD) results showed that basic CD-MOFs were cubic crystals with smooth surface and uniform sizes. The basic CD-MOFs maintained their crystalline structure after neutralization. HPLC-ELSD analysis indicated that the CD-MOF crystal size had significant influence on sucralose loading (SL). The maximal SL of micron CD-MOFs (CD-MOF-Micro) was 17.5 ± 0.9% (w/w). In contrast, 27.9 ± 1.4% of sucralose could be loaded in nanometer-sized basic CD-MOFs (CD-MOF-Nano). Molecular docking modeling showed that sucralose molecules preferentially located inside the cavities of γ-CDs pairs in CD-MOFs. Raw sucralose decomposed fast at 90°C, with 86.2 ± 0.2% of the compound degraded within only 1 h. Remarkably, sucralose stability was dramatically improved after loading in neutralized CD-MOFs, with only 13.7 ± 0.7% degradation at 90°C within 24 h.

Conclusions

CD-MOFs efficiently incorporated sucralose and maintained its integrity upon heating at elevated temperatures.

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Abbreviations

CD-MOFs:

Cyclodextrin metal organic frameworks

CTAB:

Cetyl trimethyl ammonium bromide

DSC:

Differential scanning calorimetry

EtOH:

Ethanol

HPLC-ELSD:

High performance liquid chromatography with evaporative light-scattering detection

MeOH:

Methanol

PXRD:

Powder X-ray diffraction

TGA:

Thermogravimetric analysis

γ-CD:

γ-cyclodextrin

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors are grateful for the financial support from the National Natural Science Foundation of China (No. 81430087) and National Science and Technology Major Project (2013ZX09402103).

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Author notes

    Authors and Affiliations

    1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China

      Nana Lv, Xiaonan Xu, Xue Li, Dawei Chen & Jiwen Zhang

    2. Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501 of Haike Road, Shanghai, 201210, China

      Nana Lv, Tao Guo, Botao Liu, Caifen Wang, Vikaramjeet Singh, Xiaonan Xu & Jiwen Zhang

    3. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, 201418, China

      Botao Liu

    4. Institute of Moléculaires Sciences d’Orsay, UMR CNRS 8214, Université Paris Sud, Université Paris-Saclay, 91400, Orsay, France

      Xue Li & Ruxandra Gref

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    1. Nana Lv
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    Correspondence to Dawei Chen, Ruxandra Gref or Jiwen Zhang.

    Additional information

    Equally contributing authors (N.L. for drug loading, experiments other than HPLC and preparation of the manuscript; T.G. for molecular simulation; B.L. for CD-MOFs preparation; C.W. for HPLC method establishment and validation).

    Nana Lv, Tao Guo, Botao Liu and Caifen Wang contributed equally to this work.

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    Lv, N., Guo, T., Liu, B. et al. Improvement in Thermal Stability of Sucralose by γ-Cyclodextrin Metal-Organic Frameworks. Pharm Res 34, 269–278 (2017). https://doi.org/10.1007/s11095-016-2059-1

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    • DOI: https://doi.org/10.1007/s11095-016-2059-1

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