Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks

Xiaojin Chen; Tao Guo; Kaikai Zhang; Jiacai Chen; Caifen Wang; Xiaohong Ren; Qin Wang; Yingchao Yang; Chongjing Liu; Wen Tan; Shuangying Gui; Li Wu; Jiwen Zhang

Acta Pharmaceutica Sinica B (Sep 2021)

Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks

Xiaojin Chen,
Tao Guo,
Kaikai Zhang,
Jiacai Chen,
Caifen Wang,
Xiaohong Ren,
Qin Wang,
Yingchao Yang,
Chongjing Liu,
Wen Tan,
Shuangying Gui,
Li Wu,
Jiwen Zhang

Affiliations

Xiaojin Chen: Anhui University of Traditional Chinese Medicine, Anhui 230000, China; Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
Tao Guo: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
Kaikai Zhang: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Jiacai Chen: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; Nanjing University of Traditional Chinese Medicine, Nanjing 210000, China
Caifen Wang: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
Xiaohong Ren: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
Qin Wang: Anhui University of Traditional Chinese Medicine, Anhui 230000, China; Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
Yingchao Yang: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
Chongjing Liu: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
Wen Tan: Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
Shuangying Gui: Anhui University of Traditional Chinese Medicine, Anhui 230000, China; Corresponding authors. Tel./fax: +86 21 50805901 (Jiwen Zhang); +86 21 20231980 (Li Wu); +86 551 68129123 (Shuangying Gui).
Li Wu: Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; Corresponding authors. Tel./fax: +86 21 50805901 (Jiwen Zhang); +86 21 20231980 (Li Wu); +86 551 68129123 (Shuangying Gui).
Jiwen Zhang: Anhui University of Traditional Chinese Medicine, Anhui 230000, China; Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China; Nanjing University of Traditional Chinese Medicine, Nanjing 210000, China; Corresponding authors. Tel./fax: +86 21 50805901 (Jiwen Zhang); +86 21 20231980 (Li Wu); +86 551 68129123 (Shuangying Gui).

Journal volume & issue: Vol. 11, no. 9
pp. 2914 – 2923

Abstract

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Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The in vitro release profiles of STV from STV@CD-MOF (0.5:1) were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for STV@CD-MOF (1:1) owing to nanoclusters formation. The bioavailability of STV@CD-MOF (1:1) in rats was 8.67-fold higher than that of STV, and was 1.32- and 1.27-fold higher than that of STV@CD and STV@CD-MOF (0.5:1). Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio, while the increasement in bioavailability at a high loading ratio, which was attributed to the nanocluster mechanism. This was confirmed by molecular simulation. In conclusion, CD-MOF is a promising system for STV loading, overcoming the insolubility and to improve the bioavailability of this natural compound.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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