Phospholipase A2 inhibitor-loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression

Abstract

ABSTRACTTreating osteoarthritis (OA) remains a major clinical challenge. Despite recent advances in drug discovery and development, no disease-modifying drug for knee OA has emerged with any significant clinical success, in part due to the lack of valid and responsive therapeutic targets and poor drug delivery within knee joints. In this work, we show that the amount of secretory phospholipase A2 (sPLA2) enzyme increases in articular cartilage in human and mouse OA cartilage tissues. We hypothesize that inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop a sPLA2-responsive and nanoparticle (NP)-based interventional platform for OA management, we incorporated a sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar nanoparticles (sPLA2i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA2i-NPs can be promising therapeutic agents for OA treatment.