Open AccessPhospholipase A2inhibitor–loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression
Author(s) -
Yulong Wei,
Lesan Yan,
Lijun Luo,
Tao Gui,
Bian Jang,
Ahmad Amirshaghaghi,
Tianyan You,
Andrew Tsourkas,
Ling Qin,
Zhiliang Cheng
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abe6374
Subject(s) - osteoarthritis , cartilage , drug , drug delivery , inflammation , medicine , pharmacology , materials science , pathology , nanotechnology , alternative medicine , anatomy
Treating 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 notable 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 A 2 (sPLA 2 ) enzyme increases in the articular cartilage in human and mouse OA cartilage tissues. We hypothesize that the inhibition of sPLA 2 activity may be an effective treatment strategy for OA. To develop an sPLA 2 -responsive and nanoparticle (NP)-based interventional platform for OA management, we incorporated an sPLA 2 inhibitor (sPLA 2 i) into the phospholipid membrane of micelles. The engineered sPLA 2 i-loaded micellar NPs (sPLA 2 i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA 2 i-NPs can be promising therapeutic agents for OA treatment.