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

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-1 8 (IL-1 8) 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-1 8-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. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.