Resolvin <scp>D1</scp> ‐loaded nanoliposomes promote <scp>M2</scp> macrophage polarization and are effective in the treatment of osteoarthritis
Ameya A. Dravid, Kaamini M. Dhanabalan, Smriti Agarwal, Rachit Agarwal
Abstract
Current treatments for osteoarthritis (OA) offer symptomatic relief but do not prevent or halt the disease progression. Chronic low-grade inflammation is considered a significant driver of OA. Specialized proresolution mediators are powerful agents of resolution but have a short in vivo half-life. In this study, we have engineered a Resolvin D1 (RvD1)-loaded nanoliposomal formulation (Lipo-RvD1) that targets and resolves the OA-associated inflammation. This formulation creates a depot of the RvD1 molecules that allows the controlled release of the molecule for up to 11 days in vitro. In surgically induced mice model of OA, only controlled-release formulation of Lipo-RvD1 was able to treat the progressing cartilage damage when administered a month after the surgery, while the free drug was unable to prevent cartilage damage. We found that Lipo-RvD1 functions by damping the proinflammatory activity of synovial macrophages and recruiting a higher number of M2 macrophages at the site of inflammation. Our Lipo-RvD1 formulation was able to target and suppress the formation of the osteophytes and showed analgesic effect, thus emphasizing its ability to treat clinical symptoms of OA. Such controlled-release formulation of RvD1 could represent a patient-compliant treatment for OA.