Biomaterials Translational ›› 2024, Vol. 5 ›› Issue (3): 300-313.doi: 10.12336/biomatertransl.2024.03.006
• RESEARCH ARTICLE • Previous Articles Next Articles
Yuqi Gai1, Huaijuan Zhou2,3, Yingting Yang2, Jiatian Chen1, Bowen Chi4, Pei Li5, Yue Yin1,*(), Yilong Wang4,*(
), Jinhua Li1,3,*(
)
Received:
2024-05-31
Revised:
2024-07-10
Accepted:
2024-08-30
Online:
2024-09-28
Published:
2024-09-28
Contact:
Yue Yin,Yilong Wang,Jinhua Li
E-mail:yinyue@bit.edu.cn;yilongwang528@163.com;lijinhua@bit.edu.cn
About author:
Yue Yin, yinyue@bit.edu.cn.#Authors equally.
Gai, Y.; Zhou, H.; Yang, Y.; Chen, J.; Chi, B.; Li, P.; Yin, Y.; Wang, Y.; Li, J. Injectable body temperature responsive hydrogel for encephalitis treatment via sustained release of nano-anti-inflammatory agents. Biomater Transl. 2024, 5(3), 300-313.
Figure 1. Schematic diagram of encephalitis symptoms. (A) Encephalitis can cause varying degrees of neurological deficit in patients. (B) The accumulation of inflammatory factors in the brain of patients with encephalitis. Created with Microsoft PowerPoint 2021.
Figure 2. Schematic diagram of drug action. Preparation of an injectable chitosan-based thermosensitive hydrogel for long-term sustained drug release for the treatment of cerebral inflammation. Created with Microsoft PowerPoint 2021.CS: chitosan; SA: sodium alginate; β-GP: β-glycerophosphate.
Figure 3. Basic characterisation of materials. (A) Morphology of drug-loaded liposomes, which were uniformly spherical in shape. (B) Particle size distribution of drug-loaded liposomes. (C) Photos of hydrogel formation. (C1) Before gel formation; (C2) after gel formation. (D) Internal 3D structure of hydrogel. (D1) pure hydrogel; (D2) liposome-loaded hydrogel. The liposome-loaded hydrogel had finer and more regular cavities than pure hydrogel. (E) The mechanical properties of hydrogels. 3D: three-dimensional; G’: solid line representing the storage modulus; G”: viscous modulus.
Figure 4. Drug release from hydrogel. (A) Photograph of the gradual release of the model drug from the hydrogel. The liposomal drug group released the drug more slowly than the free drug group, and more of the drug remained stored in the liposomes. Scale bars: 500 μm. (B) Drug release curve of in the hydrogel. Data are expressed as mean ± SD. Experiments were conducted in quadruplicate. +free: free DOX-HCI in the hydrogel; +lipo: liposome DOX-HCI in the hydrogel; Dox-HCl: doxorubicin hydrochloride.
Figure 5. In vitro cell uptake biological testing. (A) Cytotoxicity tests of different experimental materials, blank gel (A1), +free (A2), and +lipo (A3). (B) Confocal image of a model drug for cell uptake, with blue for nucleus localization, red for lysosomes, and green for DOX-HCl. It can be seen that drug-loaded liposomes were more likely to be enriched in the cells. Scale bars: 50 μm. (C) Flow cytometry was used to determine the amount of model drug uptaken by cells. (C1, 2) represent the relative cell amounts of the model drug uptake by different cell groups. (C3) Cell uptake rate. Data are expressed as mean ± SD. Experiments were conducted in quadruplicate. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 (Student’s t-test). DAPI: 4’,6-diamidino-2-phenylindole; Dox-HCl: doxorubicin hydrochloride; ns: not significant.
Figure 6. In vitro phenotypic conversion of MA-c cells from the A1 subtype to the A2 subtype. (A) Cell morphology at different stages. After the effect of LPS, the cells showed obvious morphological changes and their proliferative capacity was reduced. Under the effect of DEX-HCl, the morphology and proliferation rate of the cells improved significantly. (B) Data analysis. (B1–4) qPCR result of the mRNA expression levels. (B5–8) ELISA result of typical inflammatory factors in the culture medium. (B9, 10) Western blot result. The original image is shown in Additional Figure 2. Data are expressed as mean ± SD. Experiments were conducted in quadruplicate. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 (one-way analysis of variance followed by Newman-Keuls test). +free: free DOX-HCI in the hydrogel; +lipo: liposome DOX-HCI in the hydrogel. H2-D1: histocompatibility 2, D region locus 1; H2-T23: histocompatibility 2, T region locus 23; HMGB1: high mobility group box 1; IFN-γ: interferon-γ; IL: interleukin; LPS: lipopolysaccharide; ns: not significant; S100a10: S100 calcium-binding protein A10; Tgm1: transglutaminase 1; TNF -α: tumour necrosis factor -α.
Additional Figure 1. The mRNA expression levels of inflammation-related genes were investigated under different LPS concentrations. Data are expressed as mean ± SD. Experiments were conducted in quadruplicate. *P < 0.05, **P < 0.01 (one-way analysis of variance followed by Newman-Keuls test). H2-D1: histocompatibility 2, D region locus 1; H2-T23: histocompatibility 2, T region locus 23; LPS: lipopolysaccharide; ns: not significant; S100a10: S100 calcium-binding protein A10; Tgm1: transglutaminase 1.
Additional Figure 2. The original image of HMGB1 protein expression level. +free: free drug; +lipo: liposomal drug; HMGB1: high mobility group box 1; LPS: lipopolysaccharide.
1. | Bellotti, E.; Schilling, A. L.; Little, S. R.; Decuzzi, P. Injectable thermoresponsive hydrogels as drug delivery system for the treatment of central nervous system disorders: A review. J Control Release. 2021, 329, 16-35. |
2. |
Obermeier, B.; Daneman, R.; Ransohoff, R. M. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013, 19, 1584-1596.
doi: 10.1038/nm.3407 pmid: 24309662 |
3. |
Venkatesan, A.; Michael, B. D.; Probasco, J. C.; Geocadin, R. G.; Solomon, T. Acute encephalitis in immunocompetent adults. Lancet. 2019, 393, 702-716.
doi: S0140-6736(18)32526-1 pmid: 30782344 |
4. |
GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017, 16, 877-897.
doi: S1474-4422(17)30299-5 pmid: 28931491 |
5. | Cheng, Y.; Tran Minh, N.; Tran Minh, Q.; Khandelwal, S.; Clapham, H. E. Estimates of Japanese Encephalitis mortality and morbidity: A systematic review and modeling analysis. PLoS Negl Trop Dis. 2022, 16, e0010361. |
6. | World Health Organization. Why encephalitis matters? Report of the virtual meeting, 28-29 June 2022. https://www.who.int/publications/i/item/9789240069176. Accessed July 13, 2024. |
7. |
GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019, 18, 459-480.
doi: S1474-4422(18)30499-X pmid: 30879893 |
8. | Nosadini, M.; Thomas, T.; Eyre, M.; Anlar, B.; Armangue, T.; Benseler, S. M.; Cellucci, T.; Deiva, K.; Gallentine, W.; Gombolay, G.; Gorman, M. P.; Hacohen, Y.; Jiang, Y.; Lim, B. C.; Muscal, E.; Ndondo, A.; Neuteboom, R.; Rostásy, K.; Sakuma, H.; Sharma, S.; Tenembaum, S. N.; Van Mater, H. A.; Wells, E.; Wickstrom, R.; Yeshokumar, A. K.; Irani, S. R.; Dalmau, J.; Lim, M.; Dale, R. C. International consensus recommendations for the treatment of pediatric NMDAR antibody encephalitis. Neurol Neuroimmunol Neuroinflamm. 2021, 8, e1052. |
9. | Smeyne, R. J.; Noyce, A. J.; Byrne, M.; Savica, R.; Marras, C. Infection and risk of Parkinson's disease. J Parkinsons Dis. 2021, 11, 31-43. |
10. |
Ray, S. T. J.; Abdel-Mannan, O.; Sa, M.; Fuller, C.; Wood, G. K.; Pysden, K.; Yoong, M.; McCullagh, H.; Scott, D.; McMahon, M.; Thomas, N.; Taylor, M.; Illingworth, M.; McCrea, N.; Davies, V.; Whitehouse, W.; Zuberi, S.; Guthrie, K.; Wassmer, E.; Shah, N.; Baker, M. R.; Tiwary, S.; Tan, H. J.; Varma, U.; Ram, D.; Avula, S.; Enright, N.; Hassell, J.; Ross Russell, A. L.; Kumar, R.; Mulholland, R. E.; Pett, S.; Galea, I.; Thomas, R. H.; Lim, M.; Hacohen, Y.; Solomon, T.; Griffiths, M. J.; Michael, B. D.; Kneen, R.; CoroNerve study group. Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study. Lancet Child Adolesc Health. 2021, 5, 631-641.
doi: 10.1016/S2352-4642(21)00193-0 pmid: 34273304 |
11. |
Pilotto, A.; Masciocchi, S.; Volonghi, I.; Crabbio, M.; Magni, E.; De Giuli, V.; Caprioli, F.; Rifino, N.; Sessa, M.; Gennuso, M.; Cotelli, M. S.; Turla, M.; Balducci, U.; Mariotto, S.; Ferrari, S.; Ciccone, A.; Fiacco, F.; Imarisio, A.; Risi, B.; Benussi, A.; Premi, E.; Focà E.; Caccuri, F.; Leonardi, M.; Gasparotti, R.; Castelli, F.; Zanusso, G.; Pezzini, A.; Padovani, A. Clinical presentation and outcomes of severe acute respiratory syndrome coronavirus 2-related encephalitis: the ENCOVID multicenter study. J Infect Dis. 2021, 223, 28-37.
doi: 10.1093/infdis/jiaa609 pmid: 32986824 |
12. |
Matthews, E.; Beckham, J. D.; Piquet, A. L.; Tyler, K. L.; Chauhan, L.; Pastula, D. M. Herpesvirus-associated encephalitis: an update. Curr Trop Med Rep. 2022, 9, 92-100.
doi: 10.1007/s40475-022-00255-8 pmid: 36186545 |
13. |
Stahl, J. P.; Mailles, A. Herpes simplex virus encephalitis update. Curr Opin Infect Dis. 2019, 32, 239-243.
doi: 10.1097/QCO.0000000000000554 pmid: 30921087 |
14. | Gurgel Assis, M. S.; Fernandes Pedrosa, T. C.; de Moraes, F. S.; Caldeira, T. G.; Pereira, G. R.; de Souza, J.; Ruela, A. L. M. Novel insights to enhance therapeutics with acyclovir in the management of herpes simplex encephalitis. J Pharm Sci. 2021, 110, 1557-1571. |
15. | Nance, E.; Pun, S. H.; Saigal, R.; Sellers, D. L. Drug delivery to the central nervous system. Nat Rev Mater. 2022, 7, 314-331. |
16. | Wang, T.; Lei, H.; Li, X.; Yang, N.; Ma, C.; Li, G.; Gao, X.; Ge, J.; Liu, Z.; Cheng, L.; Chen, G. Magnetic targeting nanocarriers combined with focusing ultrasound for enhanced intracerebral hemorrhage therapy. Small. 2023, 19, e2206982. |
17. | Yokel, R. A. Nanoparticle brain delivery: a guide to verification methods. Nanomedicine (Lond). 2020, 15, 409-432. |
18. | Liu, J.; Sun, M.; Li, Z.; Xiang, H.; Wang, Q.; Xin, X.; Shen, Y. Catalytic nanoreactors promote GLUT1-mediated BBB permeation by generating nitric oxide for potentiating glioblastoma ferroptosis. Chem Eng J. 2024, 483, 149233. |
19. | Chen, Y. X.; Wei, C. X.; Lyu, Y. Q.; Chen, H. Z.; Jiang, G.; Gao, X. L. Biomimetic drug-delivery systems for the management of brain diseases. Biomater Sci. 2020, 8, 1073-1088. |
20. | Zhang, T. T.; Li, W.; Meng, G.; Wang, P.; Liao, W. Strategies for transporting nanoparticles across the blood-brain barrier. Biomater Sci. 2016, 4, 219-229. |
21. |
Ren, X.; Xu, R.; Xu, C.; Su, J. Harnessing exosomes for targeted therapy: strategy and application. Biomater Transl. 2024, 5, 46-58.
doi: 10.12336/biomatertransl.2024.01.005 URL |
22. |
Guo, H.; Guo, M.; Xia, X.; Shao, Z. Membrane-coated nanoparticles as a biomimetic targeted delivery system for tumour therapy. Biomater Transl. 2024, 5, 33-45.
doi: 10.12336/biomatertransl.2024.01.004 URL |
23. | Li, J.; Zhou, H.; Liu, C.; Zhang, S.; Du, R.; Deng, Y.; Zou, X. Biomembrane-inspired design of medical micro/nanorobots: From cytomembrane stealth cloaks to cellularized Trojan horses. Aggregate. 2023, 4, e359. |
24. |
Lou, M.; Zhao, Y. Satisfactory therapy results of combining nimustine with nicardipine against glioma at advanced stage. J Cancer Res Ther. 2015, 11, 1030.
doi: 10.4103/0973-1482.154033 pmid: 26881613 |
25. |
Mitchell, M. J.; Billingsley, M. M.; Haley, R. M.; Wechsler, M. E.; Peppas, N. A.; Langer, R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2021, 20, 101-124.
doi: 10.1038/s41573-020-0090-8 pmid: 33277608 |
26. |
Li, G.; Liu, S.; Chen, Y.; Zhao, J.; Xu, H.; Weng, J.; Yu, F.; Xiong, A.; Udduttula, A.; Wang, D.; Liu, P.; Chen, Y.; Zeng, H. An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment. Nat Commun. 2023, 14, 3159.
doi: 10.1038/s41467-023-38597-0 pmid: 37258510 |
27. |
Joshi, N.; Yan, J.; Levy, S.; Bhagchandani, S.; Slaughter, K. V.; Sherman, N. E.; Amirault, J.; Wang, Y.; Riegel, L.; He, X.; Rui, T. S.; Valic, M.; Vemula, P. K.; Miranda, O. R.; Levy, O.; Gravallese, E. M.; Aliprantis, A. O.; Ermann, J.; Karp, J. M. Towards an arthritis flare-responsive drug delivery system. Nat Commun. 2018, 9, 1275.
doi: 10.1038/s41467-018-03691-1 pmid: 29615615 |
28. | Wang, C.; Yang, Y.; Cao, Y.; Liu, K.; Shi, H.; Guo, X.; Liu, W.; Hao, R.; Song, H.; Zhao, R. Nanocarriers for the delivery of antibiotics into cells against intracellular bacterial infection. Biomater Sci. 2023, 11, 432-444. |
29. | Su, Y.; Fan, X.; Pang, Y. Nano-based ocular drug delivery systems: an insight into the preclinical/clinical studies and their potential in the treatment of posterior ocular diseases. Biomater Sci. 2023, 11, 4490-4507. |
30. | Wang, Q.; Jiang, N.; Fu, B.; Huang, F.; Liu, J. Self-assembling peptide-based nanodrug delivery systems. Biomater Sci. 2019, 7, 4888-4911. |
31. |
Pape, K.; Tamouza, R.; Leboyer, M.; Zipp, F. Immunoneuropsychiatry - novel perspectives on brain disorders. Nat Rev Neurol. 2019, 15, 317-328.
doi: 10.1038/s41582-019-0174-4 pmid: 30988501 |
32. | Waltl, I.; Kalinke, U. Beneficial and detrimental functions of microglia during viral encephalitis. Trends Neurosci. 2022, 45, 158-170. |
33. | Ma, X.; Gao, F.; Su, W.; Ran, Y.; Bilalijiang, T.; Tuolhen, Y.; Tian, G.; Ye, L.; Feng, Z.; Xi, J.; Liu, Z. Multifunctional injectable hydrogel promotes functional recovery after stroke by modulating microglial polarization, angiogenesis and neuroplasticity. Chem Eng J. 2023, 464, 142520. |
34. | Zheng, W.; Zhao, K.; Song, L.; Qian, Z.; Liu, W.; Zhu, Y.; Mao, Z.; Gao, C. ROS-scavenging microgels containing PTPσ receptor modulatory peptides synergistically alleviate inflammation and promote functional recovery post stroke. Chem Eng J. 2024, 483, 149225. |
35. |
Colombo, E.; Farina, C. Astrocytes: Key Regulators of Neuroinflammation. Trends Immunol. 2016, 37, 608-620.
doi: S1471-4906(16)30072-2 pmid: 27443914 |
36. | Liu, Y.; Zhang, F.; Long, L.; Li, J.; Liu, Z.; Hu, C.; Chen, X.; Zan, X.; Xu, J.; Wang, Y. Dual-function hydrogels with sequential release of GSK3β inhibitor and VEGF inhibit inflammation and promote angiogenesis after stroke. Chem Eng J. 2022, 433, 133671. |
37. |
Mei, B.; Li, J.; Zuo, Z. Dexmedetomidine attenuates sepsis-associated inflammation and encephalopathy via central α2A adrenoceptor. Brain Behav Immun. 2021, 91, 296-314.
doi: 10.1016/j.bbi.2020.10.008 pmid: 33039659 |
38. |
Venkatesan, A.; Tunkel, A. R.; Bloch, K. C.; Lauring, A. S.; Sejvar, J.; Bitnun, A.; Stahl, J. P.; Mailles, A.; Drebot, M.; Rupprecht, C. E.; Yoder, J.; Cope, J. R.; Wilson, M. R.; Whitley, R. J.; Sullivan, J.; Granerod, J.; Jones, C.; Eastwood, K.; Ward, K. N.; Durrheim, D. N.; Solbrig, M. V.; Guo-Dong, L.; Glaser, C. A.; International Encephalitis Consortium. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013, 57, 1114-1128.
doi: 10.1093/cid/cit458 pmid: 23861361 |
39. | Najjar, S.; Pearlman, D. M.; Alper, K.; Najjar, A.; Devinsky, O. Neuroinflammation and psychiatric illness. J Neuroinflammation. 2013, 10, 43. |
40. | Wang, K.; Chen, Y.; Ahn, S.; Zheng, M.; Landoni, E.; Dotti, G.; Savoldo, B.; Han, Z. GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision. Nat Cancer. 2020, 1, 990-997. |
41. |
Tischner, D.; Reichardt, H. M. Glucocorticoids in the control of neuroinflammation. Mol Cell Endocrinol. 2007, 275, 62-70.
doi: 10.1016/j.mce.2007.03.007 pmid: 17555867 |
42. |
Zamanian, J. L.; Xu, L.; Foo, L. C.; Nouri, N.; Zhou, L.; Giffard, R. G.; Barres, B. A. Genomic analysis of reactive astrogliosis. J Neurosci. 2012, 32, 6391-6410.
doi: 10.1523/JNEUROSCI.6221-11.2012 pmid: 22553043 |
43. | Liddelow, S. A.; Guttenplan, K. A.; Clarke, L. E.; Bennett, F. C.; Bohlen, C. J.; Schirmer, L.; Bennett, M. L.; Münch, A. E.; Chung, W. S.; Peterson, T. C.; Wilton, D. K.; Frouin, A.; Napier, B. A.; Panicker, N.; Kumar, M.; Buckwalter, M. S.; Rowitch, D. H.; Dawson, V. L.; Dawson, T. M.; Stevens, B.; Barres, B. A. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017, 541, 481-487. |
44. | Sun, Y. B.; Zhao, H.; Mu, D. L.; Zhang, W.; Cui, J.; Wu, L.; Alam, A.; Wang, D. X.; Ma, D. Dexmedetomidine inhibits astrocyte pyroptosis and subsequently protects the brain in in vitro and in vivo models of sepsis. Cell Death Dis. 2019, 10, 167. |
45. | Tseng, T. C.; Tao, L.; Hsieh, F. Y.; Wei, Y.; Chiu, I. M.; Hsu, S. H. An Injectable, self-healing hydrogel to repair the central nervous system. Adv Mater. 2015, 27, 3518-3524. |
46. | Li, Q.; Shao, X.; Dai, X.; Guo, Q.; Yuan, B.; Liu, Y.; Jiang, W. Recent trends in the development of hydrogel therapeutics for the treatment of central nervous system disorders. NPG Asia Mater. 2022, 14, 14. |
47. | Zhan, W.; Wang, C. H. Convection enhanced delivery of liposome encapsulated doxorubicin for brain tumour therapy. J Control Release. 2018, 285, 212-229. |
48. | Chen, C.; Sun-Waterhouse, D.; Zhao, J.; Zhang, Y.; Waterhouse, G. I. N.; Lin, L.; Zhao, M.; Sun, W. Method for loading liposomes with soybean protein isolate hydrolysate influences the antioxidant efficiency of liposomal systems: Adding after liposomes formation or before lipid film hydration. Food Hydrocoll. 2022, 129, 107629. |
49. | Abrami, M.; Siviello, C.; Grassi, G.; Larobina, D.; Grassi, M. Investigation on the thermal gelation of Chitosan/β-Glycerophosphate solutions. Carbohydr Polym. 2019, 214, 110-116. |
50. | Tang, S.; Yang, J.; Lin, L.; Peng, K.; Chen, Y.; Jin, S.; Yao, W. Construction of physically crosslinked chitosan/sodium alginate/calcium ion double-network hydrogel and its application to heavy metal ions removal. Chem Eng J. 2020, 393, 124728. |
51. | Huang, W.; Cheng, S.; Wang, X.; Zhang, Y.; Chen, L.; Zhang, L. Noncompressible hemostasis and bone regeneration induced by an absorbable bioadhesive self-healing hydrogel. Adv Funct Mater. 2021, 31, 2009189. |
52. | Kim, H. J.; Choi, B. H.; Jun, S. H.; Cha, H. J. Sandcastle worm-inspired blood-resistant bone graft binder using a sticky mussel protein for augmented in vivo bone regeneration. Adv Healthc Mater. 2016, 5, 3191-3202. |
53. | Magdanz, V.; Khalil, I. S. M.; Simmchen, J.; Furtado, G. P.; Mohanty, S.; Gebauer, J.; Xu, H.; Klingner, A.; Aziz, A.; Medina-Sánchez, M.; Schmidt, O. G.; Misra, S. IRONSperm: sperm-templated soft magnetic microrobots. Sci Adv. 2020, 6, eaba5855. |
54. |
Ren, S.; Dai, Y.; Li, C.; Qiu, Z.; Wang, X.; Tian, F.; Zhou, S.; Liu, Q.; Xing, H.; Lu, Y.; Chen, X.; Li, N. Pharmacokinetics and pharmacodynamics evaluation of a thermosensitive chitosan based hydrogel containing liposomal doxorubicin. Eur J Pharm Sci. 2016, 92, 137-145.
doi: 10.1016/j.ejps.2016.07.002 pmid: 27388491 |
55. | Cohen, J. The immunopathogenesis of sepsis. Nature. 2002, 420, 885-891. |
56. |
Soares, D. G.; Zhang, Z.; Mohamed, F.; Eyster, T. W.; de Souza Costa, C. A.; Ma, P. X. Simvastatin and nanofibrous poly(l-lactic acid) scaffolds to promote the odontogenic potential of dental pulp cells in an inflammatory environment. Acta Biomater. 2018, 68, 190-203.
doi: S1742-7061(17)30803-6 pmid: 29294374 |
57. | Zhang, H. Y.; Wang, Y.; He, Y.; Wang, T.; Huang, X. H.; Zhao, C. M.; Zhang, L.; Li, S. W.; Wang, C.; Qu, Y. N.; Jiang, X. X. A1 astrocytes contribute to murine depression-like behavior and cognitive dysfunction, which can be alleviated by IL-10 or fluorocitrate treatment. J Neuroinflammation. 2020, 17, 200. |
58. |
Albashari, A.; He, Y.; Zhang, Y.; Ali, J.; Lin, F.; Zheng, Z.; Zhang, K.; Cao, Y.; Xu, C.; Luo, L.; Wang, J.; Ye, Q. Thermosensitive bFGF-modified hydrogel with dental pulp stem cells on neuroinflammation of spinal cord injury. ACS Omega. 2020, 5, 16064-16075.
doi: 10.1021/acsomega.0c01379 pmid: 32656428 |
59. | Li, Y.; Wang, M.; Sun, M.; Wang, X.; Pei, D.; Lei, B.; Li, A. Engineering antioxidant poly (citrate-gallic acid)-Exosome hybrid hydrogel with microglia immunoregulation for Traumatic Brain Injury-post neuro-restoration. Compos B Eng. 2022, 242, 110034. |
60. | Zhang, M.; Zhang, R.; Chen, H.; Zhang, X.; Zhang, Y.; Liu, H.; Li, C.; Chen, Y.; Zeng, Q.; Huang, G. Injectable supramolecular hybrid hydrogel delivers IL-1β-stimulated exosomes to target neuroinflammation. ACS Appl Mater Interfaces. 2023, 15, 6486-6498. |
61. | Liu, Y.; Tan, Y.; Cheng, G.; Ni, Y.; Xie, A.; Zhu, X.; Yin, C.; Zhang, Y.; Chen, T. Customized intranasal hydrogel delivering methylene blue ameliorates cognitive dysfunction against Alzheimer's disease. Adv Mater. 2024, 36, e2307081. |
62. | Yao, M.; Chen, Y.; Zhang, J.; Gao, F.; Ma, S.; Guan, F. Chitosan-based thermosensitive composite hydrogel enhances the therapeutic efficacy of human umbilical cord MSC in TBI rat model. Mater Today Chem. 2019, 14, 100192. |
63. |
Xu, D.; Qiao, T.; Wang, Y.; Wang, Q. S.; Cui, Y. L. Alginate nanogels-based thermosensitive hydrogel to improve antidepressant-like effects of albiflorin via intranasal delivery. Drug Deliv. 2021, 28, 2137-2149.
doi: 10.1080/10717544.2021.1986604 pmid: 34617853 |
64. | Mahajan, S.; Nangare, S.; Chaudhari, A.; Patil, G. Synthesis of chitosan-graphene oxide thermosensitive in situ hydrogel for nasal delivery of rasagiline mesylate: in-vitro-ex vivo characterization. J Drug Deliv Sci Technol. 2024, 95, 105549. |
65. |
Gholizadeh, H.; Cheng, S.; Pozzoli, M.; Messerotti, E.; Traini, D.; Young, P.; Kourmatzis, A.; Ong, H. X. Smart thermosensitive chitosan hydrogel for nasal delivery of ibuprofen to treat neurological disorders. Expert Opin Drug Deliv. 2019, 16, 453-466.
doi: 10.1080/17425247.2019.1597051 pmid: 30884987 |
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