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Simple preparation and greatly improved oral bioavailability: The supersaturated drug delivery system of quercetin based on PVP K30

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Abstract

Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200 nm, meanwhile induce the generation of supersaturated quercetin solution more than 12 h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids.

Graphical abstract

Quercetin supersaturated drug delivery system (QSDDS) using PVP K30 as precipitation inhibitor can maintain supersaturation and increase the oral bioavailability of free quercetin in plasma(by Figdraw)

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2021-I2M-1-071) and the Open Fund for State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process (No SKL2020M0203).

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Author notes

  1. Manzhen Li and Haowen Li contributed equally to this work.

Authors and Affiliations

  1. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing, 100193, China

    Manzhen Li, Likang Lu, Jingxin Fu, Hui Ao, Meihua Han, Yifei Guo & Xiangtao Wang

  2. PK-ADME, Pharmaron Beijing, Beijing E-Town, 100176, China

    Haowen Li

  3. Jiangsu Kanion Parmaceutical Co. Ltd, Jiangsu, Lianyungang, 222001, China

    Hongda Zhang & Zhenzhong Wang

  4. National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture and Kanion Pharmaceutical Co. Ltd., Jiangsu, Lianyungang, 222001, China

    Hongda Zhang & Zhenzhong Wang

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  1. Manzhen Li
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  2. Haowen Li
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Contributions

All authors contributed to the study conception and design. Data collection: Manzhen Li and Haowen Li; formal analysis: Manzhen Li and Likang Lu; methodology: Jingxin Fu, Hui Ao, Hongda Zhang and Haowen Li; resources and supervision: Meihua Han, Yifei Guo, Zhenzhong Wang and Xiangtao Wang; writing original draft: Manzhen Li; writing -review and editing: Xiangtao Wang and Zhenzhong Wang. All authors read and approved the final manuscript.

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Correspondence to Zhenzhong Wang or Xiangtao Wang.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of The Institute of Medicinal Plant Development (SLXD-20230202013).

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Li, M., Li, H., Lu, L. et al. Simple preparation and greatly improved oral bioavailability: The supersaturated drug delivery system of quercetin based on PVP K30. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01544-7

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