Indomethacin Loaded Dextran Stearate Polymeric Micelles Improve Adjuvant-induced Arthritis in Rats: Design and in Vivo Evaluation

Overview

Journal Inflammopharmacology

Specialty Pharmacology

Date 2020 Nov 12

PMID 33179175

Citations 8

Authors

Amir Reza Abdollahi

Farzin Firouzian

Rasool Haddadi

Alireza Nourian

Affiliations

Soon will be listed here.

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 nano-sized 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, TNF-α, 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.

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References

Alunno A, Carubbi F, Giacomelli R, Gerli R . Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets. BMC Rheumatol. 2019; 1:3. PMC: 6383595. DOI: 10.1186/s41927-017-0001-8. View

Alvarez-Lorenzo C, Blanco-Fernandez B, Puga A, Concheiro A . Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. Adv Drug Deliv Rev. 2013; 65(9):1148-71. DOI: 10.1016/j.addr.2013.04.016. View

Andersson S, Lexmuller K, Johansson A, Ekstrom G . Tissue and intracellular pH in normal periarticular soft tissue and during different phases of antigen induced arthritis in the rat. J Rheumatol. 1999; 26(9):2018-24. View

Bendele A . Animal models of rheumatoid arthritis. J Musculoskelet Neuronal Interact. 2005; 1(4):377-85. View

Bernardi A, Zilberstein A, Jager E, Campos M, Morrone F, Calixto J . Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats. Br J Pharmacol. 2009; 158(4):1104-11. PMC: 2785531. DOI: 10.1111/j.1476-5381.2009.00244.x. View

Boissier M, Semerano L, Challal S, Saidenberg-Kermanach N, Falgarone G . Rheumatoid arthritis: from autoimmunity to synovitis and joint destruction. J Autoimmun. 2012; 39(3):222-8. DOI: 10.1016/j.jaut.2012.05.021. View

Brioschi A, Zenga F, Zara G, Gasco M, Ducati A, Mauro A . Solid lipid nanoparticles: could they help to improve the efficacy of pharmacologic treatments for brain tumors?. Neurol Res. 2007; 29(3):324-30. DOI: 10.1179/016164107X187017. View

Cooles F, Isaacs J . Pathophysiology of rheumatoid arthritis. Curr Opin Rheumatol. 2011; 23(3):233-40. DOI: 10.1097/BOR.0b013e32834518a3. View

10.

Couvreur P, Barratt G, Fattal E, Legrand P, Vauthier C . Nanocapsule technology: a review. Crit Rev Ther Drug Carrier Syst. 2002; 19(2):99-134. DOI: 10.1615/critrevtherdrugcarriersyst.v19.i2.10. View

11.

Du Y, Weng Q, Yuan H, Hu F . Synthesis and antitumor activity of stearate-g-dextran micelles for intracellular doxorubicin delivery. ACS Nano. 2010; 4(11):6894-902. DOI: 10.1021/nn100927t. View

12.

Dupeyron D, Kawakami M, Ferreira A, Caceres-Velez P, Rieumont J, Azevedo R . Design of indomethacin-loaded nanoparticles: effect of polymer matrix and surfactant. Int J Nanomedicine. 2013; 8:3467-77. PMC: 3787932. DOI: 10.2147/IJN.S47621. View

13.

Feng X, Chen Y . Drug delivery targets and systems for targeted treatment of rheumatoid arthritis. J Drug Target. 2018; 26(10):845-857. DOI: 10.1080/1061186X.2018.1433680. View

14.

Fernandes R, da Silva N, Sato E . Increased myeloperoxidase plasma levels in rheumatoid arthritis. Rheumatol Int. 2011; 32(6):1605-9. DOI: 10.1007/s00296-011-1810-5. View

15.

Haddadi R, Rashtiani R . Anti-inflammatory and anti-hyperalgesic effects of milnacipran in inflamed rats: involvement of myeloperoxidase activity, cytokines and oxidative/nitrosative stress. Inflammopharmacology. 2020; 28(4):903-913. DOI: 10.1007/s10787-020-00726-2. View

16.

Henderson B, Pettipher E . Arthritogenic actions of recombinant IL-1 and tumour necrosis factor alpha in the rabbit: evidence for synergistic interactions between cytokines in vivo. Clin Exp Immunol. 1989; 75(2):306-10. PMC: 1542106. View

17.

Heo R, You D, Um W, Choi K, Jeon S, Park J . Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis. Biomaterials. 2017; 131:15-26. DOI: 10.1016/j.biomaterials.2017.03.044. View

18.

Hu Y, Cheng W, Cai W, Yue Y, Li J, Zhang P . Advances in research on animal models of rheumatoid arthritis. Clin Rheumatol. 2012; 32(2):161-5. DOI: 10.1007/s10067-012-2041-1. View

19.

Hultqvist M, Olofsson P, Gelderman K, Holmberg J, Holmdahl R . A new arthritis therapy with oxidative burst inducers. PLoS Med. 2006; 3(9):e348. PMC: 1564167. DOI: 10.1371/journal.pmed.0030348. View

20.

Kato N, Mashita Y, Kato S, Mitsufuji S, Yoshikawa T, Takeuchi K . Sildenafil, an inhibitor of phosphodiesterase subtype 5, prevents indomethacin-induced small-intestinal ulceration in rats via a NO/cGMP-dependent mechanism. Dig Dis Sci. 2008; 54(11):2346-56. DOI: 10.1007/s10620-008-0646-7. View

21.

Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I . A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005; 128(5):1172-8. DOI: 10.1053/j.gastro.2005.03.020. View