Citation: Xiuyan Li, Chongjiang Wang, Xiwu Zhang, Chengcheng Zhao, Zhihui Yang, Yi Lu, Yifan Cai, Huiping Lu, Hailong Yuan, Wei Wu, Yikang Dai. Enhanced permeation of berberine by ionic liquids for the treatment of posterior age-related macular degeneration following topical delivery[J]. Chinese Chemical Letters, ;2026, 37(7): 111714. doi: 10.1016/j.cclet.2025.111714 shu

Enhanced permeation of berberine by ionic liquids for the treatment of posterior age-related macular degeneration following topical delivery

Xiuyan Li ^{a, b} ,
Chongjiang Wang ^c ,
Xiwu Zhang ^f ,
Chengcheng Zhao ^f ,
Zhihui Yang ^e ,
Yi Lu ^c ,
Yifan Cai ^c ,
Huiping Lu ^a ,
Hailong Yuan ^{e, *,} ,
Wei Wu ^{a, c, *,} ,
Yikang Dai ^{d, *,}

a.
Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
b.
Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Harbin 150001, China
c.
School of Pharmacy, Fudan University, National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China
d.
Department of Ophthalmology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
e.
Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China
f.
Experimental Teaching and Practical Training Center, Heilongjiang University of Chinese Medicine, Harbin 150001, China

yhlpharm@126.com

wuwei@shmu.edu.cn

kangkang56@126.com

Received Date: 25 February 2025
Revised Date: 8 August 2025
Accepted Date: 12 August 2025
Available Online: 12 August 2025

Figures(4)

Age-related macular degeneration (AMD) represents a primary cause of vision loss in the elderly population. Reactive oxygen species (ROS) generation constitutes a pivotal pathogenesis mechanism in AMD. Berberine (BBR) shows therapeutic potential for dry AMD through its ability to mitigate cellular senescence and oxidative stress. However, BBR’s low transmembrane permeability severely limits corneal penetration via topic administration, creating an urgent need for novel posterior segment delivery strategies. In this study, we employed biocompatible ionic liquids (ILs) to enhance BBR permeation for posterior AMD treatment. Our approach features ocular surface pretreatment with ILs followed by topical administration of BBR solution. Comprehensive in vitro and in vivo safety assessments confirmed the biocompatibility of monoethanolamine-based IL (Mea-ILs) as ocular penetration enhancers. Trans-monolayer experiments using human corneal epithelial cells (HCECs) demonstrated that ILs enhance paracellular permeability, potentially through tight junction modulation. In vivo studies utilizing a sodium iodate-induced dry AMD mouse model revealed that pretreatment with the [monoethanolamine][citric acid] ([Mea][Ci]) IL significantly potentiated BBR's therapeutic efficacy. These findings not only expand pharmaceutical applications of ILs but also establish a safe, efficient strategy for noninvasive dry AMD therapy with BBR. Furthermore, this work provides critical insights for developing advanced penetration enhancers for posterior ocular drug delivery.
- Age-related macular degeneration,
- Ionic liquids,
- Berberine hydrochloride,
- Pharmacokinetics,
- Eye drops
1. [1]
  A. Stahl, Dtsch. Arztebl. Int. 117 (2020) 513–520.
2. [2]
  W.L. Wong, X. Su, X. Li, et al., Lancet Glob. Health 2 (2014) e106–e116. doi: 10.1016/S2214-109X(13)70145-1
3. [3]
  T.A. Cabral De Guimaraes, M.Daich Varela, M. Georgiou, et al., Br. J. Ophthalmol. 106 (2022) 297–304. doi: 10.1136/bjophthalmol-2020-318452
4. [4]
  D. Song, J. Hao, D. Fan, Front. Med. 14 (2020) 564–582. doi: 10.1007/s11684-019-0724-6
5. [5]
  Q. Chen, Phytomedicine 104 (2022) 154181. doi: 10.1016/j.phymed.2022.154181
6. [6]
  S. Li, U. Gaur, C.M. Chong, et al., Int. J. Mol. Sci. 19 (2018) 1736. doi: 10.3390/ijms19061736
7. [7]
  F. Li, Preparation and Effects of Berberine hydrochloride Nanoemulsion on Mouse Model of dry AMD, Dissertation, Jiangxi University of Chinese Medicine, Nanchang, 2024.
8. [8]
  S. Lai, Y. Wei, Q. Wu, et al., J. Nanobiotechnology 17 (2019) 64. doi: 10.22217/upi.2017.570
9. [9]
  C. Huang, Z. Zhang, J. Gu, et al., Int. J. Nanomedicine 18 (2023) 4347–4363. doi: 10.2147/ijn.s417750
10. [10]
  N. Alsabeelah, V. Kumar, J. Food Biochem. 46 (2022) e14361.
11. [11]
  M. Reibaldi, T. Avitabile, F. Bandello, et al., J. Clin. Med. 8 (2019) 1031. doi: 10.3390/jcm8071031
12. [12]
  X. Chen, Z. Li, C. Yang, et al., Asian J. Pharm. Sci. 19 (2024) 100900.
13. [13]
  E. Beaven, R. Kumar, J.M. An, et al., Adv. Drug Deliv. Rev. 204 (2024) 115157. doi: 10.1016/j.addr.2023.115157
14. [14]
  Y. Lu, Y. Ma, W. Wu, MedComm Biomater. Appl. 3 (2024) e81.
15. [15]
  L. Zhang, Z. Dong, S. Yu, et al., Chin. Chem. Lett. 35 (2024) 109101. doi: 10.1016/j.cclet.2023.109101
16. [16]
  Y. Li, Q. Yu, Y. Lu, et al., Int. J. Pharm. 667 (2024) 125006. doi: 10.1016/j.ijpharm.2024.125006
17. [17]
  B. Xie, Q. Jiang, F. Zhu, et al., Chin. Chem. Lett. 36 (2025) 110508. doi: 10.1016/j.cclet.2024.110508
18. [18]
  B. Grassiri, A. Mezzetta, G. Maisetta, et al., Int. J. Mol. Sci. 24 (2023) 2714. doi: 10.3390/ijms24032714
19. [19]
  J. Wang, B. Li, J. Tang, et al., ACS Pharmacol. Transl. Sci. 5 (2022) 752–760. doi: 10.1021/acsptsci.2c00024
20. [20]
  Q. Yu, X. Wu, Y. Lu, et al., ACS Appl. Bio Mater. 7 (2024) 2899–2910. doi: 10.1021/acsabm.3c01295
21. [21]
  Y. Li, X. Wu, Q. Zhu, et al., Int. J. Pharm. 569 (2019) 118584. doi: 10.1016/j.ijpharm.2019.118584
22. [22]
  Y. Li, Q. Yu, Y. Lu, et al., Drug Deliv. Transl. Res. 15 (2025) 1693–1706. doi: 10.1007/s13346-024-01705-8
23. [23]
  X. Wu, Z. Chen, Y. Li, et al., Int. J. Pharm. 558 (2019) 380–387.
24. [24]
  X. Wu, J. Xuan, Q. Yu, et al., Pharm. Res. 39 (2022) 2421–2430. doi: 10.1007/s11095-022-03238-6
25. [25]
  K. Liu, W. Liu, Z. Dong, et al., Bioeng. Transl. Med. 8 (2023) e10405. doi: 10.1002/btm2.10405
26. [26]
  K.B. Wróblewska, B. Milanowski, M. Kucińska, et al., Pharmaceuticals 14 (2021) 849. doi: 10.3390/ph14090849
27. [27]
  Q.M. Qi, S. Mitragotri, J. Control. Release (2019) 162–169 311-312.
28. [28]
  S. Reichl, C. Kölln, M. Hahne, et al., Expert Opin. Drug Metab. Toxicol. 7 (2011) 559–578. doi: 10.1517/17425255.2011.562195
29. [29]
  S. Reichl, J. Pharm. Pharmacol. 60 (2008) 299–307. doi: 10.1211/jpp.60.3.0004
30. [30]
  S. Dey, Expert Opin. Drug Metab. Toxicol. 7 (2011) 529–532. doi: 10.1517/17425255.2011.570334
31. [31]
  D. Song, J. Song, C. Wang, et al., Exp. Eye Res. 145 (2016) 1–9. doi: 10.1155/2016/6182769
1. [1]
  Hao-Cong Li , Ming Zhang , Qiyan Lv , Kai Sun , Xiao-Lan Chen , Lingbo Qu , Bing Yu . Homogeneous catalysis and heterogeneous separation: Ionic liquids as recyclable photocatalysts for hydroacylation of olefins. Chinese Chemical Letters, 2025, 36(2): 110579-. doi: 10.1016/j.cclet.2024.110579
2. [2]
  Jiajia Wang , XinXin Ge , Yajing Xiang , Xiaoliang Qi , Ying Li , Hangbin Xu , Erya Cai , Chaofan Zhang , Yulong Lan , Xiaojing Chen , Yizuo Shi , Zhangping Li , Jianliang Shen . An ionic liquid functionalized sericin hydrogel for drug-resistant bacteria-infected diabetic wound healing. Chinese Chemical Letters, 2025, 36(2): 109819-. doi: 10.1016/j.cclet.2024.109819
3. [3]
  Mengyu Chen , Qinglin Zhou , Tianyun Qin , Ningyao Sun , Yuxi Chen , Yuwei Gong , Xingyi Li , Jinsong Liu . An ionic liquid-reinforced gelatin hydrogel with strong adhesion, antibacterial and anti-inflammatory properties for treating oral ulcers. Chinese Chemical Letters, 2025, 36(7): 110441-. doi: 10.1016/j.cclet.2024.110441
4. [4]
  Mu-Xuan Wu , Li-Ling Su , Shu-Yu Sun , Chen-Xi Bi , Zhao Zheng , Wen-Jun Feng , Bo-Quan Li , Xue-Qiang Zhang , Jia-Qi Huang . Improving the uniformity of lithium deposition via ionic liquid additives for long-cycling lithium–sulfur batteries. Chinese Chemical Letters, 2026, 37(7): 111330-. doi: 10.1016/j.cclet.2025.111330
5. [5]
  Luyu Zhang , Zirong Dong , Shuai Yu , Guangyue Li , Weiwen Kong , Wenjuan Liu , Haisheng He , Yi Lu , Wei Wu , Jianping Qi . Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes (CLNs) for enhanced intranasal siRNA delivery. Chinese Chemical Letters, 2024, 35(7): 109101-. doi: 10.1016/j.cclet.2023.109101
6. [6]
  Yidan Mao , Bingyu Li , Shuailing Ma , Siwen Cui , Zihan Zhang , Pinwen Zhu , Kongsheng Qi , Xiaodong Li , Weiwei Dong , Wei Luo , Rajeev Ahuja , Dexin Yang , Tian Cui . Metal diborides as robust and highly stable electrodes for efficient electrocatalytic reduction of CO₂ to CO in ionic liquid-based electrolytes. Chinese Chemical Letters, 2026, 37(4): 111675-. doi: 10.1016/j.cclet.2025.111675
7. [7]
  Shiwen Song , Mingyang Zhao , Xiangrong Song , Huaidong Yu , Xin Xu , Dong Sun , Jingkai Gu . Unraveling metabolic complexity of multi-payload PEG-irinotecan prodrug: A deconvolution-based LC-Q-TOF MS approach for preclinical pharmacokinetic characterization. Chinese Chemical Letters, 2026, 37(2): 112099-. doi: 10.1016/j.cclet.2025.112099
8. [8]
  Xin Xu , Huan Yang , Jiachong Chi , Xiangjun Meng , Jingkai Gu . Full-profile bioanalysis of polydisperse macromolecular hydroxyethyl starch 130/0.4 in rat plasma via LC-IS-CID coupled with MRM. Chinese Chemical Letters, 2026, 37(4): 111703-. doi: 10.1016/j.cclet.2025.111703
9. [9]
  Zhibin Ren , Shan Li , Xiaoying Liu , Guanghao Lv , Lei Chen , Jingli Wang , Xingyi Li , Jiaqing Wang . Penetrating efficiency of supramolecular hydrogel eye drops: Electrostatic interaction surpasses ligand-receptor interaction. Chinese Chemical Letters, 2024, 35(11): 109629-. doi: 10.1016/j.cclet.2024.109629
10. [10]
  Lijuan Wang , Yuping Ning , Jian Li , Sha Luo , Xiongfei Luo , Ruiwen Wang . Enhancing the Advanced Nature of Natural Product Chemistry Laboratory Courses with New Research Findings: A Case Study of the Application of Berberine Hydrochloride in Photodynamic Antimicrobial Films. University Chemistry, 2024, 39(11): 241-250. doi: 10.12461/PKU.DXHX202403017
11. [11]
  Lijuan Wang , Yuping Ning , Sha Luo . A green approach to natural products chemistry experiments: optimization and improvement of berberine hydrochloride preparation. University Chemistry, 2026, 41(4): 424-432. doi: 10.12461/PKU.DXHX202503120
12. [12]
  Qiang Zhang , Yuanbiao Huang , Rong Cao . Imidazolium-Based Materials for CO₂ Electroreduction. Acta Physico-Chimica Sinica, 2024, 40(4): 2306040-0. doi: 10.3866/PKU.WHXB202306040
13. [13]
  Jing Liu , Ming Li , Jian Zhang , Xinyu Li , Yuqing Zheng , Xu Hou . Physicochemical design of magneto-responsive confined interfaces for manipulation of nonmagnetic liquids. Chinese Chemical Letters, 2025, 36(8): 111206-. doi: 10.1016/j.cclet.2025.111206
14. [14]
  Fei-Yan Gao , Yan Wu , Ling Yang , Zhong-Yi Ma , Yi Chen , Xiao-Man Mao , Xu-Fei Bian , Pei Tang , Chong Li . Orally delivered berberine derivatives for dual therapy in diabetic complications with MRSA infections. Chinese Chemical Letters, 2025, 36(4): 109917-. doi: 10.1016/j.cclet.2024.109917
15. [15]
  Xuebing Jiang , Siyi Wang , Li Zhang , Xian Jiang , Maling Gou . Lidocaine hydrochloride loaded isomaltulose microneedles for efficient local anesthesia of the skin. Chinese Chemical Letters, 2024, 35(4): 108686-. doi: 10.1016/j.cclet.2023.108686
16. [16]
  Luyao Guan , Zhaoxin Wang , Shengkai Li , Phouphien Keoingthong , Zhuo Chen . CoPt graphitic nanozyme enabled naked-eye identification and colorimetric/fluorescent dual-mode detection of phenylenediamine isomers. Chinese Chemical Letters, 2026, 37(2): 111323-. doi: 10.1016/j.cclet.2025.111323
17. [17]
  Qihan Lin , Jiabin Xing , Yue-Yang Liu , Gang Wu , Shi-Jia Liu , Hui Wang , Wei Zhou , Zhan-Ting Li , Dan-Wei Zhang . taBOX: A water-soluble tetraanionic rectangular molecular container for conjugated molecules and taste masking for berberine and palmatine. Chinese Chemical Letters, 2024, 35(5): 109119-. doi: 10.1016/j.cclet.2023.109119
18. [18]
  Liping Zhao , Xixi Guo , Zhimeng Zhang , Xi Lu , Qingxuan Zeng , Tianyun Fan , Xintong Zhang , Fenbei Chen , Mengyi Xu , Min Yuan , Zhenjun Li , Jiandong Jiang , Jing Pang , Xuefu You , Yanxiang Wang , Danqing Song . Novel berberine derivatives as adjuvants in the battle against Acinetobacter baumannii: A promising strategy for combating multi-drug resistance. Chinese Chemical Letters, 2024, 35(10): 109506-. doi: 10.1016/j.cclet.2024.109506
19. [19]
  Liangbo Zhang , Jun Cheng , Yahui Shi , Kunjie Hou , Qi An , Jingyi Li , Baohui Cui , Fei Chen . Efficient removal of tetracycline hydrochloride by ZnO/HNTs composites under visible light: Kinetics, degradation pathways and mechanism. Chinese Chemical Letters, 2025, 36(7): 110400-. doi: 10.1016/j.cclet.2024.110400
20. [20]
  Yu Wang , Changjiang Lu , Danhua Jiao , Fei Wang , Xiaojian Gong , Tianhua Yu , Anping Wang , Chong-Chen Wang . Efficient degradation of tetracycline hydrochloride via high-redox S-scheme MOF-on-MOF heterojunction catalyst. Chinese Chemical Letters, 2026, 37(6): 111979-. doi: 10.1016/j.cclet.2025.111979

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(12)
HTML views(0)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142