Citation: Yue Wang, Zhongxin Duan, Huabin Zhang, Xia Liu, Qingyang Lu, Hua Li, Yunchu Zhang, Jiaqi Zheng, Wenyi Zhan, Mingze Du, Xifeng Zhang, Xiang Gao, Yunxiang Ji. Intranasal delivery of rosiglitazone-loaded chitosan nanoparticles promotes erythrocyte phagocytosis and alleviates brain injury after intracerebral hemorrhage[J]. Chinese Chemical Letters, ;2026, 37(12): 112336. doi: 10.1016/j.cclet.2025.112336 shu

Intranasal delivery of rosiglitazone-loaded chitosan nanoparticles promotes erythrocyte phagocytosis and alleviates brain injury after intracerebral hemorrhage

Yue Wang ^{a, 1} ,
Zhongxin Duan ^{a, 1} ,
Huabin Zhang ^{c, 1} ,
Xia Liu ^a ,
Qingyang Lu ^a ,
Hua Li ^a ,
Yunchu Zhang ^a ,
Jiaqi Zheng ^b ,
Wenyi Zhan ^a ,
Mingze Du ^d ,
Xifeng Zhang ^a ,
Xiang Gao ^{a, *,} ,
Yunxiang Ji ^{c, *,}

a.
Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
b.
West China School of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China
c.
Department of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China
d.
School of Medical Technology, Xuzhou Medical University, Xuzhou 221004, China

xianggao@scu.edu.cn

jiyunxiang@gzhmu.edu.cn

Received Date: 25 November 2025
Revised Date: 25 December 2025
Accepted Date: 28 December 2025
Available Online: 30 December 2025

Figures(5)

Intracerebral hemorrhage (ICH) is a severe condition caused by the rupture of cerebral blood vessels and subsequent blood entry into the brain parenchyma, characterized by high mortality and poor prognosis. The formation of hematoma and the release of erythrocyte lysis products following ICH are critical factors contributing to brain injury. Rosiglitazone (RSG), a thiazolidinedione drug, has demonstrated therapeutic potential in neurological disorders. However, the clinical translation of RSG for ICH is limited by its poor water solubility, low blood-brain barrier (BBB) permeability, and off-target organ toxicity such as hepatotoxicity and nephrotoxicity. In this study, we synthesized an amphiphilic ternary copolymer by covalently conjugating poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) with chitosan (CS). This polymer, designated as PEG-PLA-CS, was utilized to encapsulate RSG, forming positively charged nanoparticles (RSG@CS-NPs) to enhance mucoadhesion and transepithelial permeability. In two distinct mouse models of ICH, intranasal administration of RSG@CS-NPs enhanced erythrocyte phagocytosis by microglia and macrophages, which in turn reduced the release of cytotoxic lysis products and promoted hematoma resolution. Consequently, this treatment attenuated hematoma volume, BBB damage, and neuronal injury, leading to the amelioration of neurological deficits. This study provides a novel perspective for ICH treatment.
- Nanoparticles,
- Rosiglitazone,
- Chitosan,
- Intranasal delivery,
- Intracerebral hemorrhage
1. [1]
  T. Liu, W. Jiang, M. Zhang, et al., MedComm 6 (2025) e70436. doi: 10.1002/mco2.70436
2. [2]
  J. Magid-Bernstein, R. Girard, S. Polster, et al., Circ. Res. 130 (2022) 1204–1229. doi: 10.1161/circresaha.121.319949
3. [3]
  V.L. Feigin, B.A. Stark, C.O. Johnson, et al., Lancet Neurol. 20 (2021) 795–820. doi: 10.1016/S1474-4422(21)00252-0
4. [4]
  A. Wolsink, M.P. Cliteur, C.J. van Asch, et al., Lancet Reg. Health Eur. 49 (2025) 101180. doi: 10.1016/j.lanepe.2024.101180
5. [5]
  W. Yu, E. Gong, B. Liu, et al., Chin. Chem. Lett. 34 (2023) 108205. doi: 10.1016/j.cclet.2023.108205
6. [6]
  C. Cordonnier, A. Demchuk, W. Ziai, C.S. Anderson, Lancet 392 (2018) 1257–1268. doi: 10.1016/S0140-6736(18)31878-6
7. [7]
  K. Shi, D.C. Tian, Z.G. Li, et al., Lancet Neurol. 18 (2019) 1058–1066. doi: 10.1016/S1474-4422(19)30078-X
8. [8]
  L. Fan, L. Jin, T. Tang, et al., Theranostics 14 (2024) 283–303. doi: 10.7150/thno.90370
9. [9]
  L. Puy, A.R. Parry-Jones, E.C. Sandset, et al., Nat. Rev. Dis. Primers 9 (2023) 14. doi: 10.1038/s41572-023-00424-7
10. [10]
  C.F. Chang, J. Massey, A. Osherov, et al., Stroke 51 (2020) 612–618. doi: 10.1161/strokeaha.119.027037
11. [11]
  H.J. Deng, Y.H. Xu, K. Wu, et al., Theranostics 15 (2025) 2487–2509. doi: 10.7150/thno.103701
12. [12]
  Z. Luo, Z. Sheng, L. Hu, et al., EBioMedicine 101 (2024) 104993. doi: 10.1016/j.ebiom.2024.104993
13. [13]
  C.F. Chang, B.A. Goods, M.H. Askenase, et al., J. Clin. Invest. 128 (2018) 607–624.
14. [14]
  Y. Zheng, Y. Li, X. He, et al., Theranostics 15 (2025) 6628–6650. doi: 10.7150/thno.113764
15. [15]
  R. Hiradate, I.A. Khalil, A. Matsuda, et al., J. Control. Release 329 (2021) 665–675. doi: 10.1016/j.jconrel.2020.10.002
16. [16]
  E. Wang, R. Han, M. Wu, et al., Chin. Chem. Lett. 35 (2024) 108361. doi: 10.1016/j.cclet.2023.108361
17. [17]
  W. Cui, J. Yang, C. Tu, et al., Cell Death Dis. 15 (2024) 350. doi: 10.1038/s41419-024-06737-z
18. [18]
  J. Zhou, J. Tang, C. Zhang, et al., Free Radic. Biol. Med. 220 (2024) 271–287. doi: 10.1016/j.freeradbiomed.2024.05.014
19. [19]
  M. Ahmadian, J.M. Suh, N. Hah, et al., Nat. Med. 19 (2013) 557–566. doi: 10.1038/nm.3159
20. [20]
  L. Wang, H. Deng, J. Control. Release 387 (2025) 114221. doi: 10.1016/j.jconrel.2025.114221
21. [21]
  H. Bhardwaj, R.K. Jangde, Next Nanotechnol. 2 (2023) 100013. doi: 10.1016/j.nxnano.2023.100013
22. [22]
  Y. Xu, X. Yan, F. Zhang, et al., ACS Nano 19 (2025) 30046–30059. doi: 10.1021/acsnano.5c05354
23. [23]
  L. Jin, J. Zhang, L. Nie, et al., Chin. Chem. Lett. 36 (2025) 110774. doi: 10.1016/j.cclet.2024.110774
24. [24]
  Y. Chen, X. Yang, J. Li, et al., J. Control. Release 381 (2025) 113604. doi: 10.1016/j.jconrel.2025.113604
25. [25]
  C.P. Costa, J.N. Moreira, J.M. Sousa Lobo, A.C. Silva, Acta Pharm. Sin. B 11 (2021) 925–940. doi: 10.1016/j.apsb.2021.02.012
26. [26]
  Z. Duan, W. Zhou, S. He, et al., Small Methods 8 (2024) e2400304. doi: 10.1002/smtd.202400304
27. [27]
  D. Wu, Q. Chen, X. Chen, et al., Signal Transduct. Target. Ther. 8 (2023) 217. doi: 10.1038/s41392-023-01481-w
28. [28]
  I. Drath, F. Richter, M. Feja, Transl. Neurodegener. 14 (2025) 23. doi: 10.1186/s40035-025-00481-w
29. [29]
  Y. Qiu, S. Huang, L. Peng, et al., MedComm 6 (2025) e70213. doi: 10.1002/mco2.70213
30. [30]
  Y. Zhuang, X. Du, L. Yang, et al., Small 20 (2024) e2403564. doi: 10.1002/smll.202403564
31. [31]
  D.D. Ojeda-Hernández, S. Velasco-Lozano, J.M. Fraile, et al., Acta Biomater. 188 (2024) 157–168. doi: 10.1016/j.actbio.2024.09.002
32. [32]
  Y. Xu, X. Yan, T. Wei, et al., Nano Lett. 23 (2023) 10522–10531. doi: 10.1021/acs.nanolett.3c03419
33. [33]
  R. Liu, C. Luo, Z. Pang, et al., Chin. Chem. Lett. 34 (2023) 107518. doi: 10.1016/j.cclet.2022.05.032
34. [34]
  M.B. McGuckin, J. Wang, R. Ghanma, et al., J. Control. Release 345 (2022) 334–353. doi: 10.1016/j.jconrel.2022.03.012
35. [35]
  A.R. Clementino, G. Pellegrini, S. Banella, et al., Mol. Pharm. 18 (2021) 3132–3146. doi: 10.1021/acs.molpharmaceut.1c00366
36. [36]
  L.B. Hu, Z.H. Chen, J.L. Lu, et al., J. Extracell. Vesicles 14 (2025) e70041. doi: 10.1002/jev2.70041
37. [37]
  J. Rashid, A. Alobaida, T.A. Al-Hilal, et al., J. Control. Release 280 (2018) 113–123. doi: 10.1016/j.jconrel.2018.04.049
38. [38]
  S. Krishna, B. Cheng, D.R. Sharma, et al., Proc. Natl. Acad. Sci. U. S. A. 118 (2021) e2103084118. doi: 10.1073/pnas.2103084118
39. [39]
  C.F. Chang, J. Wan, Q. Li, et al., Neurobiol. Dis. 103 (2017) 54–69. doi: 10.1016/j.nbd.2017.03.016
40. [40]
  Y. Jiao, S. Ren, L. Wang, G. Wu, Int. Immunopharmacol. 114 (2023) 109572. doi: 10.1016/j.intimp.2022.109572
1. [1]
  Zhongxin Duan , Yue Wang , Yunchu Zhang , Xia Liu , Wanyu Wang , Hua Li , Qingyang Lu , Chao You , Yongzhong Cheng , Cong Wu , Xiang Gao . Intranasal pterostilbene nanoparticles delivery alleviates neuroinflammation and brain injury after intracerebral hemorrhage. Chinese Chemical Letters, 2026, 37(5): 111248-. doi: 10.1016/j.cclet.2025.111248
2. [2]
  Lian Jin , Juan Zhang , Libo Nie , Yan Deng , Ghulam Jilany Khana , Nongyue He . Chitosan nanoparticles act as promising carriers of microRNAs to brain cells in neurodegenerative diseases. Chinese Chemical Letters, 2025, 36(10): 110774-. doi: 10.1016/j.cclet.2024.110774
3. [3]
  Sajid Hussain , Omer M.A. Dagah , Essam A.M.S Obaid , Peng Jin , Ovas Ahmed Dar , Muhammd Irfan , Yiming Qi , Qinghua Wu , Ming Jin , Tengli Zhang , Lei Luo . Chitosan as oral absorption enhancer and inhibitor: A comprehensive review. Chinese Chemical Letters, 2026, 37(1): 111273-. doi: 10.1016/j.cclet.2025.111273
4. [4]
  Jinjie Lu , Qikai Liu , Yuting Zhang , Yi Zhou , Yanbo Zhou . Antibacterial performance of cationic quaternary phosphonium-modified chitosan polymer in water. Chinese Chemical Letters, 2024, 35(9): 109406-. doi: 10.1016/j.cclet.2023.109406
5. [5]
  Linshan Peng , Qihang Peng , Tianxiang Jin , Zhirong Liu , Yong Qian . Highly efficient capture of thorium ion by citric acid-modified chitosan gels from aqueous solution. Chinese Chemical Letters, 2024, 35(5): 108891-. doi: 10.1016/j.cclet.2023.108891
6. [6]
  Yuwen Zhu , Xiang Deng , Yan Wu , Baode Shen , Lingyu Hang , Yuye Xue , Hailong Yuan . Formation mechanism of herpetrione self-assembled nanoparticles based on pH-driven method. Chinese Chemical Letters, 2025, 36(1): 109733-. doi: 10.1016/j.cclet.2024.109733
7. [7]
  Yujie Li , Ya-Nan Wang , Yin-Gen Luo , Hongcai Yang , Jinrui Ren , Xiao Li . Advances in synthetic biology-based drug delivery systems for disease treatment. Chinese Chemical Letters, 2024, 35(11): 109576-. doi: 10.1016/j.cclet.2024.109576
8. [8]
  Zhanzhan Feng , Shuyan Zhou , Xiao Li , Guoquan Wan , Kaiyan Xu , Zhiyong Qian . Current advances in the proteolysis-targeting chimeras (PROTACs) delivery systems. Chinese Chemical Letters, 2026, 37(12): 112338-. doi: 10.1016/j.cclet.2025.112338
9. [9]
  Liangyu Zhang , Lei Lei , Zhuangzhuang Zhao , Guizhi Yang , Kaitao Wang , Liying Wang , Ningxin Zhang , Yanjia Ai , Xinqing Ma , Guannan Liu , Meng Zhao , Jun Wu , Dongjun Lin , Chun Chen . Enhanced venetoclax delivery using l-phenylalanine nanocarriers in acute myeloid leukemia treatment. Chinese Chemical Letters, 2025, 36(6): 110316-. doi: 10.1016/j.cclet.2024.110316
10. [10]
  Bohan Chen , Liming Gong , Jing Feng , Mingji Jin , Liqing Chen , Zhonggao Gao , Wei Huang . Research advances of nanoparticles for CAR-T therapy in solid tumors. Chinese Chemical Letters, 2024, 35(9): 109432-. doi: 10.1016/j.cclet.2023.109432
11. [11]
  Wei Su , Xiaoyan Luo , Peiyuan Li , Ying Zhang , Chenxiang Lin , Kang Wang , Jianzhuang Jiang . Phthalocyanine self-assembled nanoparticles for type Ⅰ photodynamic antibacterial therapy. Chinese Chemical Letters, 2024, 35(12): 109522-. doi: 10.1016/j.cclet.2024.109522
12. [12]
  Zhiyuan Huang , Fangqiu Fu , Chaoqiang Deng , Shiyang Wu , Mingxuan Huang , Xianyi Sha , Ming Q Wei , Zhiwen Zhang , Yang Zhang . Strategies of designing lymph nodes-targeting nanoparticles for cancer immunotherapy. Chinese Chemical Letters, 2026, 37(9): 111993-. doi: 10.1016/j.cclet.2025.111993
13. [13]
  Yiran Tao , Chunlei Dai , Zhaoxiang Xie , Xinru You , Kaiwen Li , Jun Wu , Hai Huang . Redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer. Chinese Chemical Letters, 2024, 35(8): 109170-. doi: 10.1016/j.cclet.2023.109170
14. [14]
  Tianxia Chen , Yunhui Chen , Weiwei Li , Peipei Cen , Yan Guo , Jin Zhang , Cunding Kong , Xiangyu Liu . Fabricating AuAg-nanoparticles/ZIF-8 composites for selective detection and efficient extraction of dinitroaniline pesticides. Chinese Chemical Letters, 2025, 36(8): 110214-. doi: 10.1016/j.cclet.2024.110214
15. [15]
  Yihao Zhang , Yang Jiao , Xianchao Jia , Qiaojia Guo , Chunying Duan . Highly effective self-assembled porphyrin MOCs nanomaterials for enhanced photodynamic therapy in tumor. Chinese Chemical Letters, 2024, 35(5): 108748-. doi: 10.1016/j.cclet.2023.108748
16. [16]
  Yixin Zhang , Ting Wang , Jixiang Zhang , Pengyu Lu , Neng Shi , Liqiang Zhang , Weiran Zhu , Nongyue He . Formation mechanism for stable system of nanoparticle/protein corona and phospholipid membrane. Chinese Chemical Letters, 2024, 35(4): 108619-. doi: 10.1016/j.cclet.2023.108619
17. [17]
  Keyang Li , Yanan Wang , Yatao Xu , Guohua Shi , Sixian Wei , Xue Zhang , Baomei Zhang , Qiang Jia , Huanhua Xu , Liangmin Yu , Jun Wu , Zhiyu He . Flash nanocomplexation (FNC): A new microvolume mixing method for nanomedicine formulation. Chinese Chemical Letters, 2024, 35(10): 109511-. doi: 10.1016/j.cclet.2024.109511
18. [18]
  Fereshte Hassanzadeh-Afruzi , Mina Azizi , Iman Zare , Ehsan Nazarzadeh Zare , Anwarul Hasan , Siavash Iravani , Pooyan Makvandi , Yi Xu . Advanced metal-organic frameworks-polymer platforms for accelerated dermal wound healing. Chinese Chemical Letters, 2024, 35(11): 109564-. doi: 10.1016/j.cclet.2024.109564
19. [19]
  Shenglan Zhou , Haijian Li , Hongyi Gao , Ang Li , Tian Li , Shanshan Cheng , Jingjing Wang , Jitti Kasemchainan , Jianhua Yi , Fengqi Zhao , Wengang Qu . Recent advances in metal-loaded MOFs photocatalysts: From single atom, cluster to nanoparticle. Chinese Chemical Letters, 2025, 36(1): 110142-. doi: 10.1016/j.cclet.2024.110142
20. [20]
  Mengdie Li , Shundong Cai , Hongjin Li , Yuhang Cheng , Jinfa Ye , Lang Ke , Yun Han , Min Su , Gang Liu , Chengchao Chu . Nanotherapeutics for ocular posterior segment diseases therapy: Towards its advances and challenges. Chinese Chemical Letters, 2026, 37(5): 111392-. doi: 10.1016/j.cclet.2025.111392

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(3)
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