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Targeted Delivery Of Morin, A Dietary Bioflavanol Encapsulated Mannosylated Liposomes To The Macrophages Of Adjuvant‐induced Arthritis Rats Inhibits Inflammatory Immune Response And Osteoclastogenesis

Farhath Sultana, M. Neog, M. Rasool
Published 2017 · Chemistry, Medicine

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&NA; The purpose of the study was to develop a liposomal drug delivery system for morin, a dietary polyphenol, in order to target the synovial macrophages and investigate the remission of disease severity in the adjuvant‐induced arthritic (AIA) rats. To do so, mannose decorated liposomal morin (ML‐Morin) was prepared using the thin film hydration method and the physicochemical properties were characterized. The particle size and zeta potential of liposomal morin (L‐Morin) was found to be 127.9 nm ± 2.6 and −24.5 mV ± 0.76, whereas ML‐Morin showed an increased value of 132.5 nm ± 5.2 and −54.8 mV ± 0.67 respectively. Further, the drug entrapment efficiency (% EE) of ML‐Morin was found 86.7 ± 3.8%. To understand the efficacy of L‐Morin, ML‐Morin over free‐Morin; cellular uptake, production and expression of pro‐inflammatory mediators, osteoclastogenic factors, and transcription factors were evaluated in primarily isolated synovial and spleen macrophages. Interestingly, confocal microscopic images showed an increased uptake of ML‐Morin in the synovial and spleen macrophages than L‐morin. In addition, ML‐Morin significantly suppressed the production and mRNA expression of pro‐inflammatory cytokines (TNF‐&agr;, IL‐1&bgr;, IL‐6, and IL‐17), angiogenic factors (VEGF), an inflammatory enzyme (iNOS), and transcription factor (NF‐&kgr;B‐p65). Furthermore, the protein expression of TNF‐&agr;, IL‐1&bgr;, IL‐6, IL‐17, RANKL, STAT‐3, and p‐STAT‐3 was found to decrease with increased osteoprotegerin (OPG) expression in the ML‐Morin targeted macrophages. Thus, our findings endorsed that, ML‐Morin preferential internalization into the macrophages of arthritic rats effectively inhibited the inflammatory immune response and osteoclastogenesis better than the dexamethasone palmitate encapsulated mannosylated liposomes (ML‐DP), a reference drug as evidenced by clinical and histological analysis. Graphical abstract Figure. No caption available.
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