Indomethacin loaded dextran stearate polymeric micelles improve adjuvant-induced arthritis in rats: design and in vivo e
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Inflammopharmacology
ORIGINAL ARTICLE
Indomethacin loaded dextran stearate polymeric micelles improve adjuvant‑induced arthritis in rats: design and in vivo evaluation Amir Reza Abdollahi1 · Farzin Firouzian2 · Rasool Haddadi1 · Alireza Nourian3 Received: 19 June 2020 / Accepted: 25 October 2020 © Springer Nature Switzerland AG 2020
Abstract Background Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that can effectively control the pain and inflammation caused by rheumatoid arthritis (RA), but its usage is limited due to severe adverse effects. For this reason, making more specific formulations of this drug can be considered. The aim of the present study was designing a novel nanosized indomethacin delivery system. Materials and methods Indomethacin-loaded dextran stearate polymeric micelles were prepared by dialysis method. Particle size and zeta potential of micelles were measured by a zeta sizer instrument. Drug release from micelles was investigated in phosphate buffer medium pH 7.4 and then the best formulation regarding physical properties and drug release was selected for animal studies. Arthritis was induced by complete Freund’s adjuvant injection in rats. Then, the animals were randomly assigned into the model, the indomethacin solution and the polymeric micelles groups. The clinical effects of polymeric micelle formulation were assessed by measuring arthritis index, animal paw edema and measuring biochemical parameters including myeloperoxidase (MPO) activity, lipid peroxidation (LPO), glutathione (GSH), total antioxidant capacity (TAC), TNF-α, IL-17 and IL-1β. Results Paw edema was attenuated following the administration of indomethacin-loaded polymeric micelles. Based on the findings of the present study, the use of indomethacin-loaded polymeric micelles could improve inflammatory symptoms, decrease arthritis index and decrease the diameter of the paw in arthritic rats in a significant manner (p ≤ 0.05). In addition, the use of polymeric micelles like indomethacin solution significantly reduced (p ≤ 0.05) the activity of MPO, LPO, TNFα, IL-17 and IL-1β, and made a significant increase (p ≤ 0.05) in glutathione and TAC content and ameliorated structural changes in the paw tissue compared to the control group. Conclusion Our findings demonstrated that indomethacin-loaded dextran stearate polymeric micelles can provide more effective therapeutic effects in control of inflammation in arthritis in rat. Keywords Dextran stearate nano-micelles · Myeloperoxidase activity · Indomethacin · Rheumatoid arthritis · Inflammatory cytokines · Oxidative stress
Introduction
* Rasool Haddadi [email protected]; [email protected] 1
Department of Pharmacology and Toxicology, Medicinal Plant and Natural Products Research Center, School of Pharmacy, Hamadan University of Medical Sciences, 6517838678 Hamadan, Iran
2
Department of Pharmaceutics, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
3
Department of Pathobiology, School of Veterinary Science, Bu
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