Intra-articular treatment of temporomandibular joint osteoarthritis by injecting actively-loaded meloxicam liposomes with dual-functions of anti-inflammation and lubrication

Yingqian Zhong; Yuyu Zhou; Ruoyi Ding; Luxiang Zou; Hongyu Zhang; Xiaohui Wei; Dongmei He

doi:10.1016/j.mtbio.2023.100573

Intra-articular treatment of temporomandibular joint osteoarthritis by injecting actively-loaded meloxicam liposomes with dual-functions of anti-inflammation and lubrication

Mater Today Bio. 2023 Feb 3:19:100573. doi: 10.1016/j.mtbio.2023.100573. eCollection 2023 Apr.

Authors

Yingqian Zhong^{1

2

3}, Yuyu Zhou⁴, Ruoyi Ding^{1

2

3}, Luxiang Zou^{1

2

3}, Hongyu Zhang⁵, Xiaohui Wei⁴, Dongmei He^{1

2

3}

Affiliations

¹ Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
² Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
³ National Clinical Research Center of Stomatology, Shanghai, 200011, China.
⁴ School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁵ State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.

Abstract

Temporomandibular joint (TMJ) osteoarthritis is a common osteochondral degenerative disease which can severely affect patient's mouth opening and mastication. Meloxicam (MLX), one of the most widely used non-steroidal anti-inflammatory drugs, is the main clinical therapy for the treatment of TMJ osteoarthritis. However, the clinical effect is greatly compromised because of its poor water solubility and high lipophilicity. In the present study, we developed an actively-loaded liposomal formulation, namely MLX-Ca(AC)₂Lipo, using meglumine to enhance aqueous solubility and divalent metal (Ca²⁺) solution to improve encapsulation efficiency. By the formation of the nano-bowl shaped MLX-Ca precipitates inside the liposomes, MLX-Ca(AC)₂Lipo successfully achieved an optimal encapsulation efficiency as high as 98.4% compared with previous passive loading method (60.6%). Additionally, MLX-Ca(AC)₂Lipo maintained stable, and the slow drug release not only prolonged the duration of drug efficacy but also improved bioavailability. It was shown in the in vitro and in vivo tests that MLX-Ca(AC)₂Lipo downregulated the synthesis of the inflammatory factors (such as prostaglandin-E2) and as a consequence reduced chondrocytes apoptosis and extracellular matrix degeneration. Furthermore, the intra-articular injection of MLX-Ca(AC)₂Lipo enhanced bioinspired lubrication of TMJ, protecting the cartilage from progressive wear. In summary, MLX-Ca(AC)₂Lipo with dual-functions of anti-inflammation and lubrication is a promising nanomedicine for the treatment of TMJ osteoarthritis by intra-articular injection.

Keywords: Active drug loading; Intra-articular injection; Liposomes; Lubrication; Osteoarthritis.