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Traditional treatments using diclofenac (DCF) as an anti\u2010inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA\u2010DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA\u2010DCF) as the MNs tips and then modifying the surface of MNs tips with a self\u2010adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti\u2010inflammatory cell tests and therapeutic animal experiments, down\u2010regulating the expression levels of pro\u2010inflammatory factors and alleviating articular cartilage destruction.<\/jats:p>","DOI":"10.1002\/smll.202307281","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T23:46:23Z","timestamp":1705362383000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Lubricating Microneedles System with Multistage Sustained Drug Delivery for the Treatment of Osteoarthritis"],"prefix":"10.1002","volume":"20","author":[{"given":"Kexin","family":"Chen","sequence":"first","affiliation":[{"name":"Center of Digital Dentistry\/Department of Prosthodontics Peking University School and Hospital of Stomatology National Center of 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