Nordihydroguaiaretic acid microparticles are effective in the treatment of osteoarthritis

Dhanabalan, KM and Padhan, B and Dravid, AA and Agarwal, S and Pancheri, NM and Lin, A and Willet, NJ and Padmanabhan, AK and Agarwal, R (2024) Nordihydroguaiaretic acid microparticles are effective in the treatment of osteoarthritis. In: Journal of Materials Chemistry B .

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Abstract

Several disease-modifying osteoarthritis (OA) drugs have emerged, but none have been approved for clinical use due to their systemic side effects, short half-life, and rapid clearance from the joints. Nordihydroguaiaretic acid (NDGA), a reactive oxygen species (ROS) scavenger and autophagy inducer, could be a potential treatment for OA. In this report, we show for the first time that sustained delivery of NDGA through polymeric microparticles maintains therapeutic concentrations of drug in the joint and ameliorates post-traumatic OA (PTOA) in a mouse model. In vitro treatment of oxidatively stressed primary chondrocytes from OA patients using NDGA-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (NDGA-MP) inhibited 15-lipoxygenase, induced autophagy, prevented chondrosenescence, and sustained matrix production. In vivo intra-articular delivery of NDGA-MP was non-toxic and had prolonged retention time (up to 35 days) in murine knee joints. Intra-articular therapy using NDGA-MP effectively reduced cartilage damage and reduced pain in the surgery-induced PTOA mouse model. Our studies open new avenues to modulate the immune environment and treat post-traumatic OA using ROS quenchers and autophagy inducers. © 2024 The Royal Society of Chemistry.

Item Type:	Journal Article
Publication:	Journal of Materials Chemistry B
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs to the publisher.
Keywords:	Arthroplasty; Cartilage; Controlled drug delivery; Drug interactions; Medicinal chemistry; Neodymium alloys; Reactive oxygen species; Targeted drug delivery, Autophagy; Clinical use; Half lives; Mice models; Micro particles; Nordihydroguaiaretic acid; Polymeric microparticles; Post-traumatic osteoarthritis; Reactive oxygen species; Side effect, Joints (anatomy)
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	22 Oct 2024 20:31
Last Modified:	22 Oct 2024 20:31
URI:	http://eprints.iisc.ac.in/id/eprint/86628

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