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已发表论文
甘草蛋白基纳米粒子可提高芍药苷的口服生物利用度和镇痛效果
Authors Yang X, Guo Q, Dong Y, Wang H, Dang M, Sun Y, Gao Y, Bai D
Received 14 May 2025
Accepted for publication 15 October 2025
Published 14 November 2025 Volume 2025:20 Pages 13781—13795
DOI https://doi.org/10.2147/IJN.S532397
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Lijie Grace Zhang
Xiaoyun Yang,1,* Qin Guo,1,* Yingying Dong,1,* Huanhuan Wang,2 Mengya Dang,1 Yangyang Sun,1 Yuan Gao,1 Dong Bai1
1Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2School of Basic Medicine, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yuan Gao, Email gaoyuan_0714@163.com Dong Bai, Email baidong2000@126.com
Purpose: In this study, Glycyrrhiza protein (GP) derived from Glycyrrhiza uralensis Fisch was used as a carrier to prepare Glycyrrhiza protein Paeoniflorin nanoparticles (GP-PF NPs), and its analgesic effects, pharmacokinetic characteristics, and cellular uptake mechanisms were investigated to evaluate its potential to improve the bioavailability of PF.
Methods: We prepared GP-PF NPs through heating. A comprehensive structural characterization of the GP-PF NPs was conducted through particle size, zeta potential, electron microscopy, and spectroscopy studies, and their self-assembly mechanism was preliminarily elucidated through molecular dynamics and molecular docking. Subsequently, the analgesic effects of the GP-PF NPs and free PF were evaluated using an acetic acid writhing model, and the in vivo processes were analyzed using pharmacokinetic studies. Finally, the mechanism of transmembrane transport of GP-PF NPs was investigated in Caco-2 cells.
Results: The GP-PF NPs showed a consistent spherical shape with a 150 nm diameter and a zeta potential of − 84 mV, providing excellent stability. The molecular dynamics and docking results indicated that GP-PF NPs have stable molecular dynamic characteristics. In the writhing mouse models, GP-PF NPs reduced the number of writhing events compared with the PF group, indicating stronger analgesic effect. The pharmacokinetic analysis showed that the GP-PF NPs exhibited a significant 2.60-fold increase in the maximum plasma concentration of PF and a significant 0.95-fold increase in the area under the curve of PF compared with free PF (P< 0.05), demonstrating improved oral bioavailability. In vitro uptake and mechanistic studies showed that the GP-PF NPs were transported across membranes through caveolin-mediated endocytosis rather than passive diffusion, significantly improving the oral bioavailability of PF.
Conclusion: GP-PF NPs enhanced PF’s oral bioavailability and analgesic performance by increasing intestinal absorption through caveolin-dependent endocytosis. Thus, GP may be a potential carrier for increasing the oral bioavailability of PF.
Keywords: paeoniflorin, Glycyrrhiza protein, nanoparticle drug delivery, oral bioavailability enhancement, caveolin-mediated endocytosis, analgesic efficacy
1Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2School of Basic Medicine, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yuan Gao, Email gaoyuan_0714@163.com Dong Bai, Email baidong2000@126.com
Purpose: In this study, Glycyrrhiza protein (GP) derived from Glycyrrhiza uralensis Fisch was used as a carrier to prepare Glycyrrhiza protein Paeoniflorin nanoparticles (GP-PF NPs), and its analgesic effects, pharmacokinetic characteristics, and cellular uptake mechanisms were investigated to evaluate its potential to improve the bioavailability of PF.
Methods: We prepared GP-PF NPs through heating. A comprehensive structural characterization of the GP-PF NPs was conducted through particle size, zeta potential, electron microscopy, and spectroscopy studies, and their self-assembly mechanism was preliminarily elucidated through molecular dynamics and molecular docking. Subsequently, the analgesic effects of the GP-PF NPs and free PF were evaluated using an acetic acid writhing model, and the in vivo processes were analyzed using pharmacokinetic studies. Finally, the mechanism of transmembrane transport of GP-PF NPs was investigated in Caco-2 cells.
Results: The GP-PF NPs showed a consistent spherical shape with a 150 nm diameter and a zeta potential of − 84 mV, providing excellent stability. The molecular dynamics and docking results indicated that GP-PF NPs have stable molecular dynamic characteristics. In the writhing mouse models, GP-PF NPs reduced the number of writhing events compared with the PF group, indicating stronger analgesic effect. The pharmacokinetic analysis showed that the GP-PF NPs exhibited a significant 2.60-fold increase in the maximum plasma concentration of PF and a significant 0.95-fold increase in the area under the curve of PF compared with free PF (P< 0.05), demonstrating improved oral bioavailability. In vitro uptake and mechanistic studies showed that the GP-PF NPs were transported across membranes through caveolin-mediated endocytosis rather than passive diffusion, significantly improving the oral bioavailability of PF.
Conclusion: GP-PF NPs enhanced PF’s oral bioavailability and analgesic performance by increasing intestinal absorption through caveolin-dependent endocytosis. Thus, GP may be a potential carrier for increasing the oral bioavailability of PF.
Keywords: paeoniflorin, Glycyrrhiza protein, nanoparticle drug delivery, oral bioavailability enhancement, caveolin-mediated endocytosis, analgesic efficacy