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

Yulin Chen ^{a, b, 1} ,
Guangchao Wang ^{a, 1} ,
Fengjin Zhou ^{c, 1} ,
Zhifeng Yin ^{d, 1} ,
Fuming Shen ^{e, f, g} ,
Weizong Weng ^e ,
Hao Zhang ^{a, e} ,
Yingying Jiang ^{e, f, g} ,
Xinru Liu ^{e, f, g} ,
Yonghui Deng ^h ,
Yuan Chen ^{b, *,} ,
Ke Xu ^{e, f, g, i, *,} ,
Jiacan Su ^{a, e, f, g, *,}

a.
Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
b.
Department of Orthopedics and Traumatology, Nanning Hospital of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China
c.
Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710000, China
d.
Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai 200444, China
e.
Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
f.
Organoid Research Center, Shanghai University, Shanghai 200444, China
g.
National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China
h.
Department of Chemistry, Department of Gastroenterology, Zhongshan Hospital of Fudan University, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China
i.
Wenzhou Institute of Shanghai University, Wenzhou 325000, China

Cheny2801@163.com

kexu@shu.edu.cn

drsujiacan@163.com

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.
- Microsphere,
- HAMA hydrogel,
- Liposome,
- Osteoarthritis,
- TRPA1
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