Research ArticleHEALTH AND MEDICINE

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

See allHide authors and affiliations

Science Advances  07 Apr 2021:
Vol. 7, no. 15, eabe6374
DOI: 10.1126/sciadv.abe6374

Abstract

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 A2 (sPLA2) enzyme increases in the articular cartilage in human and mouse OA cartilage tissues. We hypothesize that the inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop an sPLA2-responsive and nanoparticle (NP)–based interventional platform for OA management, we incorporated an sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar NPs (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.

https://creativecommons.org/licenses/by-nc/4.0/

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

View Full Text

Stay Connected to Science Advances