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已发表论文
通过脑靶向脂质纳米载体增强槲皮素的抗抑郁功效：制备、表征及评估
Authors Chen T , Zeng M, Xiong L, Li W, Cheng Z, Wang C
Received 25 July 2025
Accepted for publication 16 December 2025
Published 26 December 2025 Volume 2025:20 Pages 15793—15811
DOI https://doi.org/10.2147/IJN.S556128
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 6
Editor who approved publication: Professor Eng San Thian
Tao Chen,1 Mingtang Zeng,2 Linjin Xiong,3 Wen Li,4 Zhichan Cheng,5 Chenglong Wang1
1Department of Pharmacy, Yibin Hospital Affiliated to Children’s Hospital of Chongqing Medical University, Yibin, Sichuan, People’s Republic of China; 2Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Pharmacy, Chengdu Hi-Tech Zone Hospital for Women and Children (Chengdu Hi-Tech Zone Hospital for Maternal and Child Healthcare), Chengdu, Sichuan, People’s Republic of China; 4School of Pharmacy, Central Nervous System Drug Key Laboratory of Sichuan Province, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Pharmacy, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of China
Correspondence: Chenglong Wang, Department of Pharmacy, Yibin Hospital Affiliated to Children’s Hospital of Chongqing Medical University, No. 108, Shangmao Road, Xuzhou District, Yibin, Sichuan, 644000, People’s Republic of China, Email 714170033@qq.com
Purpose: This study aims to develop a quercetin-loaded nanoparticles (QNP) with enhanced brain delivery capacity, which enables efficient delivery of quercetin to target brain regions under the guidance of borneol for the treatment of depression.
Methods: We prepared QNP via the thin-film dispersion method and characterized them by particle size, polydispersity index (PDI), zeta potential, morphology, release profile, and stability. Subsequently, a suite of models and assays including hemolysis test, cellular CCK-8 assay, cellular uptake experiment, and lipopolysaccharide (LPS) induced BV2 cell stress model were employed to comprehensively assess the antidepressant activity of QNP. Finally, we validated the in vivo antidepressant effect of QNP using an established depression mouse model.
Results: QNP exhibit a spheroidal shape with favorable particle size, PDI, and zeta potential. They have high encapsulation efficiency and exhibit sustained drug release capability. QNP remain stable in serum and saline solution. They maintain stability after 30 days of storage at room temperature. Results from the hemolysis test and cellular CCK-8 assay preliminarily suggested that QNP had a favorable safety profile. Additionally, cellular uptake experiments showed that the uptake rate of QNP by cells was nearly twice that of the quercetin. Assays using corticosterone- and hydrogen peroxide-induced PC12 cell injury models demonstrate that QNP exert a concentration-dependent cytoprotective effect. In the LPS-induced BV2 cell stress model, QNP exhibit superior inhibitory activity against NO and ROS compared with Qu. They also significantly inhibit IL-1β transcription. In vivo studies indicated that, compared with the first-line antidepressant fluoxetine, QNP alleviated depressive-like behaviors more effectively.
Conclusion: The lipid nanodrug delivery system QNP exhibit sustained drug release and enhanced cellular uptake. By virtue of safety and improved delivery efficiency, they multidimensionally augment the therapeutic efficacy of antidepressants. This is crucial for translating quercetin from a dietary supplement into a precision antidepressant.
Keywords: depression, quercetin, lipid nanoparticles, inflammation, oxidative stress
1Department of Pharmacy, Yibin Hospital Affiliated to Children’s Hospital of Chongqing Medical University, Yibin, Sichuan, People’s Republic of China; 2Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Pharmacy, Chengdu Hi-Tech Zone Hospital for Women and Children (Chengdu Hi-Tech Zone Hospital for Maternal and Child Healthcare), Chengdu, Sichuan, People’s Republic of China; 4School of Pharmacy, Central Nervous System Drug Key Laboratory of Sichuan Province, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Pharmacy, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of China
Correspondence: Chenglong Wang, Department of Pharmacy, Yibin Hospital Affiliated to Children’s Hospital of Chongqing Medical University, No. 108, Shangmao Road, Xuzhou District, Yibin, Sichuan, 644000, People’s Republic of China, Email 714170033@qq.com
Purpose: This study aims to develop a quercetin-loaded nanoparticles (QNP) with enhanced brain delivery capacity, which enables efficient delivery of quercetin to target brain regions under the guidance of borneol for the treatment of depression.
Methods: We prepared QNP via the thin-film dispersion method and characterized them by particle size, polydispersity index (PDI), zeta potential, morphology, release profile, and stability. Subsequently, a suite of models and assays including hemolysis test, cellular CCK-8 assay, cellular uptake experiment, and lipopolysaccharide (LPS) induced BV2 cell stress model were employed to comprehensively assess the antidepressant activity of QNP. Finally, we validated the in vivo antidepressant effect of QNP using an established depression mouse model.
Results: QNP exhibit a spheroidal shape with favorable particle size, PDI, and zeta potential. They have high encapsulation efficiency and exhibit sustained drug release capability. QNP remain stable in serum and saline solution. They maintain stability after 30 days of storage at room temperature. Results from the hemolysis test and cellular CCK-8 assay preliminarily suggested that QNP had a favorable safety profile. Additionally, cellular uptake experiments showed that the uptake rate of QNP by cells was nearly twice that of the quercetin. Assays using corticosterone- and hydrogen peroxide-induced PC12 cell injury models demonstrate that QNP exert a concentration-dependent cytoprotective effect. In the LPS-induced BV2 cell stress model, QNP exhibit superior inhibitory activity against NO and ROS compared with Qu. They also significantly inhibit IL-1β transcription. In vivo studies indicated that, compared with the first-line antidepressant fluoxetine, QNP alleviated depressive-like behaviors more effectively.
Conclusion: The lipid nanodrug delivery system QNP exhibit sustained drug release and enhanced cellular uptake. By virtue of safety and improved delivery efficiency, they multidimensionally augment the therapeutic efficacy of antidepressants. This is crucial for translating quercetin from a dietary supplement into a precision antidepressant.
Keywords: depression, quercetin, lipid nanoparticles, inflammation, oxidative stress