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Self-Assembled Micelles Improve the Oral Bioavailability of Dihydromyricetin and Anti-Acute Alcoholism Activity

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Abstract

Dihydromyricetin (DMY) is highly effective in counteracting acute alcohol intoxication. However, its poor aqueous solubility and permeability lead to the low oral bioavailability and limit its clinic application. The aim of this work is to use Solutol®HS15 (HS 15) as surfactant to develop novel micelle to enhance the oral bioavailability of DMY by improving its solubility and permeability. The DMY-loaded Solutol®HS15 micelles (DMY-Ms) were prepared by the thin-film hydration method. The particle size of DMY-Ms was 13.97 ± 0.82 nm with an acceptable polydispersity index of 0.197 ± 0.015. Upon entrapped in micelles, the solubility of DMY in water was increased more than 25-fold. The DMY-Ms had better sustained release property than that of pure DMY. In single-pass intestinal perfusion models, the absorption rate constant (Ka) and permeability coefficient (Papp) of DMY-Ms were 5.5-fold and 3.0-fold than that of pure DMY, respectively. The relative bioavailability of the DMY-Ms (AUC0–∞) was 205% compared with that of pure DMY (AUC0–∞), indicating potential for clinical application. After administering DMY-Ms, there was much lower blood alcohol level and shorter duration of the loss of righting relax (LORR) in drunk animals compared with that treated by pure DMY. In addition, the oral administration of DMY-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages in mice with alcohol-induced tissue injury. Taken together, HS 15-based micelle system greatly improves the bioavailability of DMY and represents a promising strategy for the management of acute alcoholism.

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Acknowledgements

This work was supported by the financial support from the National Natural Science Foundation of China (No. 81603045), the Major Project of Education Department in Sichuan (No. 17ZA0117), the Key Open Fund of Key Laboratory of Coarse Grain Processing, Ministry of Agriculture (Grant No. 2019CC02), the Xinglin Scholars Research Enhancement Program (Grant No. XSGG2019005), the Chun-Hui Research Project of Ministry of Education of China (Grant No.20191083-127), the Provincial University Students Innovation and Entrepreneurship Training Programs (Grant No.201813705094), and Foundation of Chengdu Medical College (Grant No. CYZYB20-11).

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  1. Jing Ye and Sha Bao contributed equally to this work.

Authors and Affiliations

  1. Institute of Materia Medica, School of Pharmacy, Chengdu Medical College, No. 783 Xindu Avenue, Chengdu, 610500, China

    Jing Ye, Sha Bao, Shiying Zhao, Yujing Zhu, Qiao Ren, Xiaohong Xu & Quan Zhang

  2. Development and Regeneration Key Lab of Sichuan Province, Department of Pathology, Department of Anatomy and Histology and Embryology, Chengdu Medical College, Chengdu, 610500, China

    Quan Zhang

  3. State Key Laboratory of Characteristic Chinese Drug Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

    Rui Li

  4. Chengdu Phyto Cosmos Biological Technology Co., Ltd, Chengdu, 610041, China

    Rui Li

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Ye, J., Bao, S., Zhao, S. et al. Self-Assembled Micelles Improve the Oral Bioavailability of Dihydromyricetin and Anti-Acute Alcoholism Activity. AAPS PharmSciTech 22, 111 (2021). https://doi.org/10.1208/s12249-021-01983-2

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