Intra‐articular injection of rapamycin microparticles prevent senescence and effectively treat osteoarthritis

Dhanabalan, Kaamini M and Dravid, Ameya A and Agarwal, Smriti and Sharath, Ramanath K and Padmanabhan, Ashok Kumar and Agarwal, Rachit (2022) Intra‐articular injection of rapamycin microparticles prevent senescence and effectively treat osteoarthritis. In: Bioengineering & Translational Medicine . ISSN 2380-6761

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Abstract

Trauma to the knee joint is associated with significant cartilage degeneration and erosion of subchondral bone, which eventually leads to osteoarthritis (OA), resulting in substantial morbidity and healthcare burden. With no disease-modifying drugs in clinics, the current standard of care focuses on symptomatic relief and viscosupplementation. Modulation of autophagy and targeting senescence pathways are emerging as potential treatment strategies. Rapamycin has shown promise in OA disease amelioration by autophagy upregulation, yet its clinical use is hindered by difficulties in achieving therapeutic concentrations, necessitating multiple weekly injections. Rapamycin-loaded in poly(lactic-co-glycolic acid) microparticles (RMPs) induced autophagy, prevented senescence, and sustained sulphated glycosaminoglycans production in primary human articular chondrocytes from OA patients. RMPs were potent, nontoxic, and exhibited high retention time (up to 35 days) in mice joints. Intra-articular delivery of RMPs effectively mitigated cartilage damage and inflammation in surgery-induced OA when administered as a prophylactic or therapeutic regimen. Together, the study demonstrates the feasibility of using RMPs as a potential clinically translatable therapy to prevent the progression of post-traumatic OA. © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.

Item Type:	Journal Article
Publication:	Bioengineering & Translational Medicine
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright of this article belongs to the John Wiley and Sons Inc.
Keywords:	autophagy; intra-articular therapy; microparticles; osteoarthritis; PLGA; rapamycin; senescence
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	23 May 2022 09:09
Last Modified:	23 May 2022 09:09
URI:	https://eprints.iisc.ac.in/id/eprint/72406

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