Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis

References

• Mangalea MR, Paez-Espino D, Kieft K., et al. Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential. Cell Host Microbe. 2021;29(5):726–739 e725. doi:10.1016/j.chom.2021.03.020
   PubMed Web of Science ®Google Scholar
• Smolen JS, Landewe RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18. doi:10.1136/ard-2022-223356
   PubMed Web of Science ®Google Scholar
• Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest. 2008;118(11):3537–3545. doi:10.1172/JCI36389
   PubMed Web of Science ®Google Scholar
• Kondo N, Kuroda T, Kobayashi D. Cytokine networks in the pathogenesis of rheumatoid arthritis. Int J Mol Sci. 2021;22:20 doi:10.3390/ijms222010922.
   Web of Science ®Google Scholar
• Jeong JC, Chung YH, Park T, et al. Safety and effectiveness of 4-week therapy with aceclofenac controlled release once a day. Sci Rep. 2022;12(1):16519. doi:10.1038/s41598-022-20633-6
   PubMed Web of Science ®Google Scholar
• Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis. 2001;60(8):729–735. doi:10.1136/ard.60.8.729
   PubMed Web of Science ®Google Scholar
• Hamed KM, Dighriri IM, Baomar AF, et al. Overview of Methotrexate Toxicity: a Comprehensive Literature Review. Cureus. 2022;14(9):e29518. doi:10.7759/cureus.29518
   PubMed Web of Science ®Google Scholar
• Xu M, Wu S, Wang Y, et al. Association between high-dose methotrexate-induced toxicity and polymorphisms within methotrexate pathway genes in acute lymphoblastic leukemia. Front Pharmacol. 2022;13:1003812. doi:10.3389/fphar.2022.1003812
   PubMed Web of Science ®Google Scholar
• Kremer JM, Genovese MC, Cannon GW, et al. Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate: a randomized, double-blind, placebo-controlled trial. Ann Internal Med. 2002;137(9):726–733. doi:10.7326/0003-4819-137-9-200211050-00007
   PubMed Web of Science ®Google Scholar
• Capell HA, Madhok R, Porter DR, et al. Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study. Ann Rheumatic Dis. 2007;66(2):235–241. doi:10.1136/ard.2006.057133
   PubMed Web of Science ®Google Scholar
• Verschueren P, De Cock D, Corluy L, et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheumatic Dis. 2015;74(1):27–34. doi:10.1136/annrheumdis-2014-205489
   PubMed Web of Science ®Google Scholar
• Zanfirescu A, Nitulescu G, Stancov G, et al. Evaluation of topical anti-inflammatory effects of a gel formulation with plantago lanceolata, Achillea millefolium, Aesculus hippocastanum and Taxodium distichum. Sci Pharm. 2020;88(2):26. doi:10.3390/scipharm88020026
   Web of Science ®Google Scholar
• Smolen JS, Avila JC, Aletaha D. Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction. Ann Rheum Dis. 2012;71(5):687–693. doi:10.1136/annrheumdis-2011-200395
   PubMed Web of Science ®Google Scholar
• Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med. 1992;327(11):749–754. doi:10.1056/NEJM199209103271101
   PubMed Web of Science ®Google Scholar
• Mazaud C, Fardet L. Relative risk of and determinants for adverse events of methotrexate prescribed at a low dose: a systematic review and meta‐analysis of randomized placebo‐controlled trials. Br J Dermatol. 2017;177(4):978–986. doi:10.1111/bjd.15377
   PubMed Web of Science ®Google Scholar
• Onda K, Honma T, Masuyama K. Methotrexate-related adverse events and impact of concomitant treatment with folic acid and tumor necrosis factor-alpha inhibitors: an assessment using the FDA adverse event reporting system. Front Pharmacol. 2023;14:1030832. doi:10.3389/fphar.2023.1030832
   PubMed Web of Science ®Google Scholar
• Garg NK, Tyagi RK, Singh B, et al. Nanostructured lipid carrier mediates effective delivery of methotrexate to induce apoptosis of rheumatoid arthritis via NF-kappaB and FOXO1. Int J Pharm. 2016;499(1–2):301–320. doi:10.1016/j.ijpharm.2015.12.061
   PubMed Web of Science ®Google Scholar
• Garg NK, Singh B, Kushwah V, et al. The ligand (s) anchored lipobrid nanoconstruct mediated delivery of methotrexate: an effective approach in breast cancer therapeutics. Nanomed Nanotechnol Biol Med. 2016;12(7):2043–2060. doi:10.1016/j.nano.2016.05.008
   PubMed Web of Science ®Google Scholar
• Garg NK, Tyagi RK, Sharma G, et al. Functionalized lipid-polymer hybrid nanoparticles mediated codelivery of methotrexate and aceclofenac: a synergistic effect in breast cancer with improved pharmacokinetics attributes. Mol Pharmaceut. 2017;14(6):1883–1897. doi:10.1021/acs.molpharmaceut.6b01148
   PubMed Web of Science ®Google Scholar
• Garg NK, Tandel N, Bhadada SK, Tyagi RK. Nanostructured lipid carrier-mediated transdermal delivery of aceclofenac hydrogel present an effective therapeutic approach for inflammatory diseases. Front Pharmacol. 2021;12:713616. doi:10.3389/fphar.2021.713616
   PubMed Web of Science ®Google Scholar
• Garg NK, Sharma G, Singh B, et al. Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): an improved dermatokinetic profile for inflammatory disorder(s). Int J Pharm. 2017;517(1–2):413–431. doi:10.1016/j.ijpharm.2016.12.010
   PubMed Web of Science ®Google Scholar
• Zewail M, Nafee N, Helmy MW, Boraie N. Coated nanostructured lipid carriers targeting the joints–An effective and safe approach for the oral management of rheumatoid arthritis. Int J Pharm. 2019;567:118447. doi:10.1016/j.ijpharm.2019.118447
   PubMed Web of Science ®Google Scholar
• Gu Y, Tang X, Yang M, Yang D, Liu J. Transdermal drug delivery of triptolide-loaded nanostructured lipid carriers: preparation, pharmacokinetic, and evaluation for rheumatoid arthritis. Int J Pharm. 2019;554:235–244. doi:10.1016/j.ijpharm.2018.11.024
   PubMed Web of Science ®Google Scholar
• Tchetverikov I, Lohmander LS, Verzijl N, et al. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis. 2005;64(5):694–698. doi:10.1136/ard.2004.022434
   PubMed Web of Science ®Google Scholar
• Gossage DL, Cieslarova B, Ap S, et al. Phase 1b study of the safety, pharmacokinetics, and disease-related outcomes of the matrix metalloproteinase-9 inhibitor andecaliximab in patients with rheumatoid arthritis. Clin. Ther. 2018;40(1):156–165. e155. doi:10.1016/j.clinthera.2017.11.011
   PubMed Web of Science ®Google Scholar
• Raeeszadeh-Sarmazdeh M, Do LD, Hritz BG. Metalloproteinases and their inhibitors: potential for the development of new therapeutics. Cells. 2020;9(5):1313. doi:10.3390/cells9051313
   PubMed Web of Science ®Google Scholar
• Garg NK, Singh B, Sharma G, et al. Development and characterization of single step self-assembled lipid polymer hybrid nanoparticles for effective delivery of methotrexate. RSC Adv. 2015;5(77):62989–62999. doi:10.1039/C5RA12459J
   Web of Science ®Google Scholar
• Jain S, Chauhan DS, Jain AK, et al., Inventors. A universal step-wise freeze drying process for lyophilization of pharmaceutical products; 2011.
   Google Scholar
• Garg NK, Sharma G, Singh B, Nirbhavane P, Katare OP. Quality by Design (QbD)-based development and optimization of a simple, robust RP HPLC method for the estimation of Methotrexate. J Liquid Chromatogr Related Technol. 2015;38(17):1629–1637. doi:10.1080/10826076.2015.1087409
   Web of Science ®Google Scholar
• Garg NK, Dwivedi P, Campbell C, Tyagi RK. Site specific/targeted delivery of gemcitabine through anisamide anchored chitosan/poly ethylene glycol nanoparticles: an improved understanding of lung cancer therapeutic intervention. Eur. J. Pharm. Sci. 2012;47(5):1006–1014. doi:10.1016/j.ejps.2012.09.012
   PubMed Web of Science ®Google Scholar
• Jain AK, Jain A, Garga NK, et al. Adapalene loaded solid lipid nanoparticles gel: an effective approach for acne treatment. Colloids Surf B. 2014;121:222–229. doi:10.1016/j.colsurfb.2014.05.041
   PubMed Web of Science ®Google Scholar
• Chen B, Li H, Ding Y, Suo H. Formation and microstructural characterization of whey protein isolate/beet pectin coacervations by laccase catalyzed cross-linking. LWT – Food Sci Technol. 2012;47(1):31–38. doi:10.1016/j.lwt.2012.01.006
   Web of Science ®Google Scholar
• de Ávila MDR, Cambero MI, Ordóñez JA, de la Hoz L, Herrero AM. Rheological behaviour of commercial cooked meat products evaluated by tensile test and texture profile analysis (TPA). Meat Sci. 2014;98(2):310–315. doi:10.1016/j.meatsci.2014.05.003
   PubMed Web of Science ®Google Scholar
• Tyagi RK, Garg NK, Jadon R, et al. Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P. falciparum surface antigen, MSP-1. Vaccine. 2015;33:4630–4638. doi:10.1016/j.vaccine.2015.06.054
   PubMed Web of Science ®Google Scholar
• Kilfoyle BE, Sheihet L, Zhang Z, Laohoo M, Kohn J, Michniak-Kohn BB. Development of paclitaxel-TyroSpheres for topical skin treatment. J Control Release. 2012;163(1):18–24. doi:10.1016/j.jconrel.2012.06.021
   PubMed Web of Science ®Google Scholar
• Raza K, Singh B, Singla S, et al. Nanocolloidal carriers of isotretinoin: antimicrobial activity against Propionibacterium acnes and dermatokinetic modeling. Mol Pharmaceut. 2013;10(5):1958–1963. doi:10.1021/mp300722f
   PubMed Web of Science ®Google Scholar
• Ramachandran S, Kota P, Ding F, Dokholyan NV. Automated minimization of steric clashes in protein structures. Proteins. 2011;79(1):261–270. doi:10.1002/prot.22879
   PubMed Web of Science ®Google Scholar
• Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455–461. doi:10.1002/jcc.21334
   PubMed Web of Science ®Google Scholar
• Liu Y, Grimm M, Dai WT, Hou MC, Xiao ZX, Cao Y. CB-Dock: a web server for cavity detection-guided protein-ligand blind docking. Acta Pharmacol. Sin. 2020;41(1):138–144. doi:10.1038/s41401-019-0228-6
   PubMed Web of Science ®Google Scholar
• DeLano WL. Pymol: an open-source molecular graphics tool. CCP4 Newsl. Protein Crystal. 2002;40(1):82–92.
   Google Scholar
• Biovia D Discovery Studio Modeling Environment, Dassault Syst. Release, San Diego; 2015:4.
   Google Scholar
• Sharma P, Singh S. Combinatorial effect of DCA and Let-7a on Triple-Negative MDA-MB-231 cells: a metabolic approach of treatment. Integr Cancer Ther. 2020;19:1534735420911437. doi:10.1177/1534735420911437
   Web of Science ®Google Scholar
• Salter M, Duffy C, Garthwaite J, Strijbos PJ. Ex vivo measurement of brain tissue nitrite and nitrate accurately reflects nitric oxide synthase activity in vivo. J Neurochem. 1996;66(4):1683–1690. doi:10.1046/j.1471-4159.1996.66041683.x
   PubMed Web of Science ®Google Scholar
• Chillingworth NL, Donaldson LF. Characterisation of a Freund’s complete adjuvant-induced model of chronic arthritis in mice. J Neurosci Methods. 2003;128(1–2):45–52. doi:10.1016/s0165-0270(03)00147-x
   PubMed Web of Science ®Google Scholar
• Gomes RP, Bressan E, Silva TM, Gevaerd MS, Tonussi CR, Domenech SC. Standardization of an experimental model suitable for studies on the effect of exercise on arthritis. Einstein. 2013;11(1):76–82. doi:10.1590/s1679-45082013000100014
   PubMedGoogle Scholar
• Geboes L, Klerck BD, Balen MV, et al. Freund’s complete adjuvant induces arthritis in mice lacking a functional interferon‐γ receptor by triggering tumor necrosis factor α–driven osteoclastogenesis. Arthritis Rheum. 2007;56(8):2595–2607. doi:10.1002/art.22791
   PubMedGoogle Scholar
• Zhang L, Chan JM, Gu FX, et al. Self-assembled lipid− polymer hybrid nanoparticles: a robust drug delivery platform. ACS nano. 2008;2(8):1696–1702. doi:10.1021/nn800275r
   PubMed Web of Science ®Google Scholar
• Chawla V, Saraf SA. Rheological studies on solid lipid nanoparticle based carbopol gels of aceclofenac. Colloids Surf B Biointerfaces. 2012;92:293–298. doi:10.1016/j.colsurfb.2011.12.006
   PubMed Web of Science ®Google Scholar
• Ghica MV, Hîrjău M, Lupuleasa D, Dinu-Pîrvu C-E. Flow and thixotropic parameters for rheological characterization of hydrogels. Molecules. 2016;21(6):786. doi:10.3390/molecules21060786
   PubMed Web of Science ®Google Scholar
• Chen MH, Wang LL, Chung JJ, Kim Y-H, Atluri P, Burdick JA. Methods to assess shear-thinning hydrogels for application as injectable biomaterials. ACS Biomater Sci Eng. 2017;3(12):3146–3160. doi:10.1021/acsbiomaterials.7b00734
   PubMed Web of Science ®Google Scholar
• Xu Y, Shrestha N, Preat V, Beloqui A. An overview of in vitro, ex vivo and in vivo models for studying the transport of drugs across intestinal barriers. Adv Drug Deliv Rev. 2021;175:113795. doi:10.1016/j.addr.2021.05.005
   PubMed Web of Science ®Google Scholar
• Tyagi RK, Miles B, Parmar R, et al. Human IDO-competent, long-lived immunoregulatory dendritic cells induced by intracellular pathogen, and their fate in humanized mice. Sci Rep. 2017;7:41083. doi:10.1038/srep41083
   PubMed Web of Science ®Google Scholar
• Riol-Blanco L, Delgado-Martin C, Sanchez-Sanchez N, et al. Immunological synapse formation inhibits, via NF-kappaB and FOXO1, the apoptosis of dendritic cells. Nat Immunol. 2009;10(7):753–760. doi:10.1038/ni.1750
   PubMed Web of Science ®Google Scholar
• Jiang Q, Yang G, Liu Q, Wang S, Cui D. Function and role of regulatory T cells in rheumatoid arthritis. Front Immunol. 2021;12:626193. doi:10.3389/fimmu.2021.626193
   PubMedGoogle Scholar
• Kanjana K, Chevaisrakul P, Matangkasombut P, Paisooksantivatana K, Lumjiaktase P. Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis. Sci Rep. 2020;10(1):19789. doi:10.1038/s41598-020-76168-1
   PubMed Web of Science ®Google Scholar
• Yan S, Kotschenreuther K, Deng S, Kofler DM. Regulatory T cells in rheumatoid arthritis: functions, development, regulation, and therapeutic potential. Cell Mol Life Sci. 2022;79(10):533. doi:10.1007/s00018-022-04563-0
   PubMed Web of Science ®Google Scholar
• Van’t Hof R, Hocking L, Wright P, Ralston S. Nitric oxide is a mediator of apoptosis in the rheumatoid joint. Rheumatology. 2000;39(9):1004–1008. doi:10.1093/rheumatology/39.9.1004
   PubMed Web of Science ®Google Scholar
• Ralston SH. Nitric oxide and bone. Immunology. 2001;103(3):255–261. doi:10.1046/j.1365-2567.2001.01261.x
   PubMed Web of Science ®Google Scholar
• Nagy G, Koncz A, Telarico T, et al. Central role of nitric oxide in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Therapy. 2010;12(3):1–6. doi:10.1186/ar3045
   Web of Science ®Google Scholar
• Weitoft T, Lind A, Larsson A, Ronnelid J, Hogman M. Exhaled nitric oxide in early rheumatoid arthritis and effects of methotrexate treatment. Sci Rep. 2022;12(1):6489. doi:10.1038/s41598-022-10334-5
   PubMedGoogle Scholar
• Lee YM, Lee S, Kim WJ. Nitric oxide scavengers based on o-phenylenediamine for the treatment of rheumatoid arthritis. Biomater Sci. 2023;11(7):2395–2404. doi:10.1039/d2bm01994a
   PubMed Web of Science ®Google Scholar
• Kokkonen H, Soderstrom I, Rocklov J, Hallmans G, Lejon K, Rantapaa Dahlqvist S. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 2010;62(2):383–391. doi:10.1002/art.27186
   PubMedGoogle Scholar
• Peake N, Khawaja K, Myers A, et al. Levels of matrix metalloproteinase (MMP)-1 in paired sera and synovial fluids of juvenile idiopathic arthritis patients: relationship to inflammatory activity, MMP-3 and tissue inhibitor of metalloproteinases-1 in a longitudinal study. Rheumatology. 2005;44(11):1383–1389. doi:10.1093/rheumatology/kei025
   PubMed Web of Science ®Google Scholar
• Czajkowska-Kosnik A, Szymanska E, Winnicka K. Nanostructured Lipid Carriers (NLC)-based gel formulations as etodolac delivery: from gel preparation to permeation study. Molecules. 2022;28:1 doi:10.3390/molecules28010235.
   PubMed Web of Science ®Google Scholar
• Silva E, Barreiros L, Segundo MA, Lima SAC, Reis S. Cellular interactions of a lipid-based nanocarrier model with human keratinocytes: unravelling transport mechanisms. Acta Biomater. 2017;53:439–449. doi:10.1016/j.actbio.2017.01.057
   PubMed Web of Science ®Google Scholar
• Cordenonsi LM, Faccendini A, Catanzaro M, et al. The role of chitosan as coating material for nanostructured lipid carriers for skin delivery of fucoxanthin. Int J Pharm. 2019;567:118487. doi:10.1016/j.ijpharm.2019.118487
   PubMedGoogle Scholar
• Wu J. The enhanced permeability and retention (epr) effect: the significance of the concept and methods to enhance its application. J Pers Med. 2021;11:8 doi:10.3390/jpm11080771.
   Web of Science ®Google Scholar
• Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun. 2018;9(1):1410. doi:10.1038/s41467-018-03705-y
   PubMed Web of Science ®Google Scholar
• Gao S, Tian B, Han J, et al. Enhanced transdermal delivery of lornoxicam by nanostructured lipid carrier gels modified with polyarginine peptide for treatment of carrageenan-induced rat paw edema. Int j Nanomed. 2019;14:6135. doi:10.2147/IJN.S205295
   PubMed Web of Science ®Google Scholar
• Garg NK, Singh B, Tyagi RK, Sharma G, Katare OP. Effective transdermal delivery of methotrexate through nanostructured lipid carriers in an experimentally induced arthritis model. Colloids Surf B. 2016;147:17–24. doi:10.1016/j.colsurfb.2016.07.046
   PubMed Web of Science ®Google Scholar
• Dissanayake K, Jayasinghe C, Wanigasekara P, Sominanda A. Potential applicability of cytokines as biomarkers of disease activity in rheumatoid arthritis: enzyme-linked immunosorbent spot assay-based evaluation of TNF-alpha, IL-1beta, IL-10 and IL-17A. PLoS One. 2021;16(1):e0246111. doi:10.1371/journal.pone.0246111
   PubMed Web of Science ®Google Scholar
• Yamada S, Nagafuchi Y, Wang M, et al. Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance. Ann Rheum Dis. 2023. doi:10.1136/ard-2022-223645
   Google Scholar
• Zhu C, Zhou J, Li T, Mu J, Jin L, Li S. Urocortin participates in LPS-induced apoptosis of THP-1 macrophages via S1P-cPLA2 signaling pathway. Eur. J. Pharmacol. 2020;887:173559. doi:10.1016/j.ejphar.2020.173559
   PubMed Web of Science ®Google Scholar
• Suzuki T, Kobayashi M, Isatsu K, et al. Mechanisms involved in apoptosis of human macrophages induced by lipopolysaccharide from actinobacillus actinomycetemcomitans in the presence of cycloheximide. Infect Immun. 2004;72(4):1856. doi:10.1128/IAI.72.4.1856-1865.2004
   PubMed Web of Science ®Google Scholar
• Green MJ, Gough AK, Devlin J, et al. Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. Rheumatology. 2003;42(1):83–88. doi:10.1093/rheumatology/keg037
   PubMed Web of Science ®Google Scholar
• Tchetverikov I, Ronday HK, van El B, et al. MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis. Ann Rheumatic Dis. 2004;63(7):881. doi:10.1136/ard.2003.013243
   PubMed Web of Science ®Google Scholar
• Hussein R, Aboukhamis I. Serum matrix metalloproteinase-3 levels monitor the therapeutic efficacy in Syrian patients with rheumatoid arthritis. Heliyon. 2023;9(3):e14008. doi:10.1016/j.heliyon.2023.e1400
   PubMed Web of Science ®Google Scholar
• Rubbert-Roth A. Methotrexate in rheumatoid arthritis—another brick in the wall. Lancet Rheumatol. 2023;5(4):e173–e175. doi:10.1016/S2665-9913(23)00069-3
   PubMedGoogle Scholar
• Kim J, Chun K, McGowan J, et al. 14-3-3zeta: a suppressor of inflammatory arthritis. Proc Natl Acad Sci U S A. 2021;118:34 doi:10.1073/pnas.2025257118.
   Web of Science ®Google Scholar
• Negi S, Tandel N, Sharma P, Kumar R, Tyagi RK. Aceclofenac and methotrexate combination therapy could influence Th1/Th17 axis to modulate rheumatoid-arthritis-induced inflammation. Drug Discov Today. 2023;28(8):103671. doi:10.1016/j.drudis.2023.103671
   PubMed Web of Science ®Google Scholar