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.