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bioRxiv · 10.1101/2023.01.21.525015

Sustained release Resolvin D1 liposomes are effective in the treatment of osteoarthritis in obese mice

Dravid, A. A.·Dhanabalan, K. M.·Naskar, S.·Vashistha, A.·Agarwal, S.·Padhan, B.·Dewani, M.·Agarwal, R.
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Abstract

Osteoarthritis (OA) is the most common joint disorder and currently affects > 500 million patients worldwide, with ~60% of them also suffering from obesity. There is no drug approved for human use that changes the course of OA progression. OA is one of the most common comorbidities of obesity, and obesity-related OA (ObOA) is a serious health concern because it shows heightened severity of tissue damage and also predominantly affects the working population. Unresolved inflammation is a major driver of ObOA, thus, resolving disease-associated inflammation is a viable strategy to treat ObOA. Resolvins are highly potent molecules that play a role in the resolution of inflammation and promote tissue healing. However, small molecules (like Resolvin D1; RvD1) have to be administered frequently or prior to injury because they lose their in vivo activity rapidly either by lymphatic clearance, or oxidation-mediated deactivation. In this study, we have encapsulated RvD1 in liposomes and established its efficacy in the mouse model of ObOA at much lower dosages than freely administered RvD1. Liposomal RvD1 (lipo-RvD1) acted as a source of the RvD1 molecules for ~11 days in vitro in synovial fluid derived from patients. When administered prophylactically or therapeutically, lipo-RvD1 suppressed cartilage damage in male C57BL/6 mice compared to untreated and free RvD1 treatments. This efficacy was achieved by increasing the proportion of the proresolution M2 macrophages over proinflammatory M1 macrophages in the synovial membrane. These results show the potential of lipo-RvD1 as an anti-OA agent. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/525015v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@141d889org.highwire.dtl.DTLVardef@1ef1753org.highwire.dtl.DTLVardef@1e463c1org.highwire.dtl.DTLVardef@15138c6_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO Mechanism of working of lipo-RvD1 in ObOA joint. C_FIG

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Dravid, A. A., Dhanabalan, K. M., Naskar, S., Vashistha, A., Agarwal, S., Padhan, B., Dewani, M., Agarwal, R.. 2023-01-22. Sustained release Resolvin D1 liposomes are effective in the treatment of osteoarthritis in obese mice. https://doi.org/10.1101/2023.01.21.525015

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