Citation: Yulin Chen, Guangchao Wang, Fengjin Zhou, Zhifeng Yin, Fuming Shen, Weizong Weng, Hao Zhang, Yingying Jiang, Xinru Liu, Yonghui Deng, Yuan Chen, Ke Xu, Jiacan Su. Targeting TRPA1 with liposome-encapsulated drugs anchored to microspheres for effective osteoarthritis treatment[J]. Chinese Chemical Letters, ;2025, 36(5): 110053. doi: 10.1016/j.cclet.2024.110053 shu

Targeting TRPA1 with liposome-encapsulated drugs anchored to microspheres for effective osteoarthritis treatment

    * Corresponding author.
    E-mail addresses: Cheny2801@163.com (Y. Chen), kexu@shu.edu.cn (K. Xu), drsujiacan@163.com (J. Su).
    1 These authors contributed equally to this work.
  • Received Date: 17 February 2024
    Revised Date: 23 May 2024
    Accepted Date: 24 May 2024
    Available Online: 26 May 2024

Figures(5)

  • Crucial for mediating inflammation and the perception of pain, the ion channel known as transient receptor potential ankyrin 1 (TRPA1) holds significant importance. It contributes to the increased production of cytokines in the inflammatory cells of cartilage affected by osteoarthritis and represents a promising target for the treatment of this condition. By leveraging the unique advantages of liposomes, a composite microsphere drug delivery system with stable structural properties and high adaptability can be developed, providing a new strategy for osteoarthritis (OA) drug therapy. The liposomes as drug reservoirs for TRPA1 inhibitors were loaded into hyaluronic acid methacrylate (HAMA) hydrogels to make hydrogel microspheres via microfluidic technology. An in vitro inflammatory chondrocyte model was established with interleukin-1β (IL-1β) to demonstrate HAMA@Lipo@HC's capabilities. A destabilization of the medial meniscus (DMM) mouse model was also created to evaluate the efficacy of intra-articular injections for treating OA. HAMA@Lipo@HC has a uniform particle-size distribution and is injectable. The drug encapsulation rate was 64.29% ± 2.58%, with a sustained release period of 28 days. Inhibition of TRPA1 via HC-030031 effectively alleviated IL-1β-induced chondrocyte inflammation and matrix degradation. In DMM model OA mice, microspheres showed good long-term sustained drug release properties, improved joint inflammation microenvironment, reduced articular cartilage damage and decreased mechanical nociceptive threshold. This research pioneers the creation of a drug delivery system tailored for delivery into the joint cavity, focusing on TRPA1 as a therapeutic target for osteoarthritis. Additionally, it offers a cutting-edge drug delivery platform aimed at addressing diseases linked to inflammation.

    1. [1]

      J.N. Katz, K.R. Arant, R.F. Loeser, JAMa 325 (2021) 568–578.  doi: 10.1001/jama.2020.22171

    2. [2]

      J. Li, W. Zhang, X. Liu, et al., Cell Prolif. 56 (2023) e13518.

    3. [3]

      F. Motta, E. Barone, A. Sica, C. Selmi, Clin. Rev. Allergy Immunol. 64 (2023) 222–238.

    4. [4]

      T. Wang, C. He, Cytokine Growth Factor Rev. 44 (2018) 38–50.

    5. [5]

      J.W. Bijlsma, F. Berenbaum, F.P. Lafeber, Lancet 377 (2011) 2115–2126.

    6. [6]

      H. Zhang, L. Wang, J. Cui, et al., Sci. Adv. 9 (2023) eabo7868.

    7. [7]

      P. Kulkarni, A. Martson, R. Vidya, S. Chitnavis, A. Harsulkar, Adv. Clin. Chem. 100 (2021) 37–90.

    8. [8]

      D.J. Hunter, J.L. Bowden, Nat. Rev. Rheumatol. 13 (2017) 703–704.  doi: 10.1038/nrrheum.2017.160

    9. [9]

      A. Nowaczyk, D. Szwedowski, I. Dallo, J. Nowaczyk, Int. J. Mol. Sci. 23 (2022) 1566.  doi: 10.3390/ijms23031566

    10. [10]

      M.P. Hellio Le Graverand-Gastineau, OsteoArthritis Cartilage. 17 (2009) 1393–1401.

    11. [11]

      L. Pang, H. Jin, Z. Lu, et al., Adv. Healthc. Mater. 12 (2023) e2300315.

    12. [12]

      K. Talavera, J.B. Startek, J. Alvarez-Collazo, et al., Physiol. Rev. 100 (2020) 725–803.  doi: 10.1152/physrev.00005.2019

    13. [13]

      J.E. Meents, C.I. Ciotu, M.J.M. Fischer, J. Neurophysiol. 121 (2019) 427–443.  doi: 10.1152/jn.00524.2018

    14. [14]

      T. Galindo, J. Reyna, A. Weyer, Pharmaceuticals 11 (2018) 105.  doi: 10.3390/ph11040105

    15. [15]

      E. Nummenmaa, M. Hämäläinen, L.J. Moilanen, et al., Arthritis Res. Ther. 18 (2016) 185.

    16. [16]

      L.J. Moilanen, M. Hämäläinen, E. Nummenmaa, et al., OsteoArthritis Cartilage. 23 (2015) 2017–2026.

    17. [17]

      M. Mitrovic, A. Shahbazian, E. Bock, M.A. Pabst, P. Holzer, Br. J. Pharmacol. 160 (2010) 1430–1442.  doi: 10.1111/j.1476-5381.2010.00794.x

    18. [18]

      L.J. Moilanen, M. Hamalainen, L. Lehtimaki, R.M. Nieminen, E. Moilanen, PLoS. One 10 (2015) e0117770.  doi: 10.1371/journal.pone.0117770

    19. [19]

      K.J. Cowan, K. Kleinschmidt-Dorr, A. Gigout, et al., Drug Discov. Today 25 (2020) 1054–1064.

    20. [20]

      L. Kou, S. Xiao, R. Sun, et al., Drug Deliv. 26 (2019) 870–885.  doi: 10.1080/10717544.2019.1660434

    21. [21]

      S. Mehta, T. He, A.G. Bajpayee, Curr. Opin. Rheumatol. 33 (2021) 94–109.  doi: 10.1097/bor.0000000000000761

    22. [22]

      S.G. Antimisiaris, A. Marazioti, M. Kannavou, et al., Adv. Drug Deliv. Rev. 174 (2021) 53–86.

    23. [23]

      X. Ji, Y. Yan, T. Sun, et al., Biomater. Sci. 7 (2019) 2716–2728.  doi: 10.1039/c9bm00201d

    24. [24]

      D. Zhou, F. Zhou, S. Sheng, et al., Drug Discov. Today 28 (2023) 103482.

    25. [25]

      X. Xue, Y. Hu, S. Wang, et al., Bioact. Mater. 12 (2022) 327–339.

    26. [26]

      J. Yang, Y. Zhu, F. Wang, et al., Chem. Eng. J. 400 (2020) 126004.

    27. [27]

      Q. Yang, Y. Wang, T. Liu, et al., ACS Nano 16 (2022) 18366–18375.  doi: 10.1021/acsnano.2c06261

    28. [28]

      Z. Xu, G. Liu, P. Liu, et al., Acta Biomater. 147 (2022) 147–157.

    29. [29]

      R. Ziadlou, S. Rotman, A. Teuschl, et al., Mater. Sci. Eng. C Mater. Biol. Appl. 120 (2021) 111701.

    30. [30]

      G. Li, S. Liu, Y. Chen, et al., Nat. Commun. 14 (2023) 3159.

    31. [31]

      C. Shen, J. Wang, G. Li, et al., Bioact. Mater. 35 (2024) 429–444.

    32. [32]

      Y. Tao, Y. Chen, S. Wang, et al., Compos. Part B: Eng. 247 (2022) 110288.

    33. [33]

      H. Daraee, A. Etemadi, M. Kouhi, S. Alimirzalu, A. Akbarzadeh, Artif. Cells Nanomed. Biotechnol. 44 (2016) 381–391.  doi: 10.3109/21691401.2014.953633

    34. [34]

      Z. Zhou, P. Song, Y. Wu, et al., Mater. Horiz. 11 (2024) 1465–1483.  doi: 10.1039/d3mh01581e

    35. [35]

      E. Nummenmaa, M. Hämäläinen, A. Pemmari, et al., Int. J. Mol. Sci. 22 (2020) 87.  doi: 10.3390/ijms22010087

    36. [36]

      S. Yin, L. Zhang, L. Ding, et al., J. Inflamm. 15 (2018) 27.

    37. [37]

      T. Ohtsuki, O.F. Hatipoglu, K. Asano, et al., Int. J. Mol. Sci. 21(2020) 3140.  doi: 10.3390/ijms21093140

    38. [38]

      M.Y. Ansari, N. Ahmad, T.M. Haqqi, Biomed. Pharmacother. 129 (2020) 110452.

    39. [39]

      W. Hu, Y. Chen, C. Dou, S. Dong, Ann. Rheum. Dis. 80 (2021) 413–422.  doi: 10.1136/annrheumdis-2020-218089

    1. [1]

      J.N. Katz, K.R. Arant, R.F. Loeser, JAMa 325 (2021) 568–578.  doi: 10.1001/jama.2020.22171

    2. [2]

      J. Li, W. Zhang, X. Liu, et al., Cell Prolif. 56 (2023) e13518.

    3. [3]

      F. Motta, E. Barone, A. Sica, C. Selmi, Clin. Rev. Allergy Immunol. 64 (2023) 222–238.

    4. [4]

      T. Wang, C. He, Cytokine Growth Factor Rev. 44 (2018) 38–50.

    5. [5]

      J.W. Bijlsma, F. Berenbaum, F.P. Lafeber, Lancet 377 (2011) 2115–2126.

    6. [6]

      H. Zhang, L. Wang, J. Cui, et al., Sci. Adv. 9 (2023) eabo7868.

    7. [7]

      P. Kulkarni, A. Martson, R. Vidya, S. Chitnavis, A. Harsulkar, Adv. Clin. Chem. 100 (2021) 37–90.

    8. [8]

      D.J. Hunter, J.L. Bowden, Nat. Rev. Rheumatol. 13 (2017) 703–704.  doi: 10.1038/nrrheum.2017.160

    9. [9]

      A. Nowaczyk, D. Szwedowski, I. Dallo, J. Nowaczyk, Int. J. Mol. Sci. 23 (2022) 1566.  doi: 10.3390/ijms23031566

    10. [10]

      M.P. Hellio Le Graverand-Gastineau, OsteoArthritis Cartilage. 17 (2009) 1393–1401.

    11. [11]

      L. Pang, H. Jin, Z. Lu, et al., Adv. Healthc. Mater. 12 (2023) e2300315.

    12. [12]

      K. Talavera, J.B. Startek, J. Alvarez-Collazo, et al., Physiol. Rev. 100 (2020) 725–803.  doi: 10.1152/physrev.00005.2019

    13. [13]

      J.E. Meents, C.I. Ciotu, M.J.M. Fischer, J. Neurophysiol. 121 (2019) 427–443.  doi: 10.1152/jn.00524.2018

    14. [14]

      T. Galindo, J. Reyna, A. Weyer, Pharmaceuticals 11 (2018) 105.  doi: 10.3390/ph11040105

    15. [15]

      E. Nummenmaa, M. Hämäläinen, L.J. Moilanen, et al., Arthritis Res. Ther. 18 (2016) 185.

    16. [16]

      L.J. Moilanen, M. Hämäläinen, E. Nummenmaa, et al., OsteoArthritis Cartilage. 23 (2015) 2017–2026.

    17. [17]

      M. Mitrovic, A. Shahbazian, E. Bock, M.A. Pabst, P. Holzer, Br. J. Pharmacol. 160 (2010) 1430–1442.  doi: 10.1111/j.1476-5381.2010.00794.x

    18. [18]

      L.J. Moilanen, M. Hamalainen, L. Lehtimaki, R.M. Nieminen, E. Moilanen, PLoS. One 10 (2015) e0117770.  doi: 10.1371/journal.pone.0117770

    19. [19]

      K.J. Cowan, K. Kleinschmidt-Dorr, A. Gigout, et al., Drug Discov. Today 25 (2020) 1054–1064.

    20. [20]

      L. Kou, S. Xiao, R. Sun, et al., Drug Deliv. 26 (2019) 870–885.  doi: 10.1080/10717544.2019.1660434

    21. [21]

      S. Mehta, T. He, A.G. Bajpayee, Curr. Opin. Rheumatol. 33 (2021) 94–109.  doi: 10.1097/bor.0000000000000761

    22. [22]

      S.G. Antimisiaris, A. Marazioti, M. Kannavou, et al., Adv. Drug Deliv. Rev. 174 (2021) 53–86.

    23. [23]

      X. Ji, Y. Yan, T. Sun, et al., Biomater. Sci. 7 (2019) 2716–2728.  doi: 10.1039/c9bm00201d

    24. [24]

      D. Zhou, F. Zhou, S. Sheng, et al., Drug Discov. Today 28 (2023) 103482.

    25. [25]

      X. Xue, Y. Hu, S. Wang, et al., Bioact. Mater. 12 (2022) 327–339.

    26. [26]

      J. Yang, Y. Zhu, F. Wang, et al., Chem. Eng. J. 400 (2020) 126004.

    27. [27]

      Q. Yang, Y. Wang, T. Liu, et al., ACS Nano 16 (2022) 18366–18375.  doi: 10.1021/acsnano.2c06261

    28. [28]

      Z. Xu, G. Liu, P. Liu, et al., Acta Biomater. 147 (2022) 147–157.

    29. [29]

      R. Ziadlou, S. Rotman, A. Teuschl, et al., Mater. Sci. Eng. C Mater. Biol. Appl. 120 (2021) 111701.

    30. [30]

      G. Li, S. Liu, Y. Chen, et al., Nat. Commun. 14 (2023) 3159.

    31. [31]

      C. Shen, J. Wang, G. Li, et al., Bioact. Mater. 35 (2024) 429–444.

    32. [32]

      Y. Tao, Y. Chen, S. Wang, et al., Compos. Part B: Eng. 247 (2022) 110288.

    33. [33]

      H. Daraee, A. Etemadi, M. Kouhi, S. Alimirzalu, A. Akbarzadeh, Artif. Cells Nanomed. Biotechnol. 44 (2016) 381–391.  doi: 10.3109/21691401.2014.953633

    34. [34]

      Z. Zhou, P. Song, Y. Wu, et al., Mater. Horiz. 11 (2024) 1465–1483.  doi: 10.1039/d3mh01581e

    35. [35]

      E. Nummenmaa, M. Hämäläinen, A. Pemmari, et al., Int. J. Mol. Sci. 22 (2020) 87.  doi: 10.3390/ijms22010087

    36. [36]

      S. Yin, L. Zhang, L. Ding, et al., J. Inflamm. 15 (2018) 27.

    37. [37]

      T. Ohtsuki, O.F. Hatipoglu, K. Asano, et al., Int. J. Mol. Sci. 21(2020) 3140.  doi: 10.3390/ijms21093140

    38. [38]

      M.Y. Ansari, N. Ahmad, T.M. Haqqi, Biomed. Pharmacother. 129 (2020) 110452.

    39. [39]

      W. Hu, Y. Chen, C. Dou, S. Dong, Ann. Rheum. Dis. 80 (2021) 413–422.  doi: 10.1136/annrheumdis-2020-218089

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