{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:47:32Z","timestamp":1777880852274,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"National Council of Technological and Scientific Development (CNPq)","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"National Council of Technological and Scientific Development (CNPq)","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"National Council of Technological and Scientific Development (CNPq)","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"National Council of Technological and Scientific Development (CNPq)","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"National Council of Technological and Scientific Development (CNPq)","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"National Council of Technological and Scientific Development (CNPq)","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"Research Support Foundation of the State of Rio Grande do Sul (FAPERGS)","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"Research Support Foundation of the State of Rio Grande do Sul (FAPERGS)","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"Research Support Foundation of the State of Rio Grande do Sul (FAPERGS)","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"Research Support Foundation of the State of Rio Grande do Sul (FAPERGS)","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"Research Support Foundation of the State of Rio Grande do Sul (FAPERGS)","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"Research Support Foundation of the State of Rio Grande do Sul (FAPERGS)","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP, Brazil)","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP, Brazil)","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP, Brazil)","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP, Brazil)","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP, Brazil)","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP, Brazil)","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"CNPq","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"CNPq","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"CNPq","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"CNPq","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"CNPq","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"CNPq","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"CNPq\/PQ","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"CNPq\/PQ","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"CNPq\/PQ","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"CNPq\/PQ","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"CNPq\/PQ","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"CNPq\/PQ","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"PRONEX\/FAPERGS\/CNPq","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"PRONEX\/FAPERGS\/CNPq","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"PRONEX\/FAPERGS\/CNPq","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"PRONEX\/FAPERGS\/CNPq","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"PRONEX\/FAPERGS\/CNPq","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"PRONEX\/FAPERGS\/CNPq","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas (FAPEAM)","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas (FAPEAM)","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas (FAPEAM)","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas (FAPEAM)","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas (FAPEAM)","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas (FAPEAM)","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["#2014\/50928-2"],"award-info":[{"award-number":["#2014\/50928-2"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["#465687\/2014-8"],"award-info":[{"award-number":["#465687\/2014-8"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["305343\/2019-0"],"award-info":[{"award-number":["305343\/2019-0"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["#16\/2551-0000467-6"],"award-info":[{"award-number":["#16\/2551-0000467-6"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["#008\/2021"],"award-info":[{"award-number":["#008\/2021"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["#005\/2022"],"award-info":[{"award-number":["#005\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Diclofenac is the most prescribed nonsteroidal anti-inflammatory drug worldwide and is used to relieve pain and inflammation in inflammatory arthritis. Diclofenac is associated with serious adverse effects, even in regular-dose regimens. Drug delivery systems can overcome this issue by reducing adverse effects and optimizing their efficacy. This study evaluated the activity of lipid-core nanocapsules loaded with diclofenac (DIC-LNCs) in an experimental model of adjuvant-induced arthritis. The diclofenac nanoformulation was obtained via self-assembly. A stereological analysis approach was applied for the morphological quantification of the volume, density, and cellular profile count of the metatarsophalangeal joints of rats. Proinflammatory cytokines and biochemical profiles were also obtained. Our results showed that the diclofenac nanocapsule DIC-LNCs were able to reduce arthritis compared with the control group and the DIC group. DIC-LNCs efficiently reduced proinflammatory cytokines, C-reactive protein, and xanthine oxidase levels. Additionally, DIC-LNCs reduced the loss of synoviocytes and chondrocytes compared with the DIC (p &lt; 0.05) and control groups (p &lt; 0.05). These data suggest that DIC-LNCs have anti-arthritic activity and preserve joint components, making them promising for clinical use.<\/jats:p>","DOI":"10.3390\/molecules28135219","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:54:41Z","timestamp":1688604881000},"page":"5219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Anti-Arthritic Activity of Diclofenac Lipid-Core Nanocapsules: Stereological Analysis Showing More Protection of Deep Joint Components"],"prefix":"10.3390","volume":"28","author":[{"given":"Nathalie Marte","family":"Ure\u00f1a","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o e Imunologia B\u00e1sica e Aplicada, Universidade Federal do Amazonas, Manaus 69077-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cati\u00fascia Padilha","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Stanis\u00e7uaski","family":"Guterres","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-1807","authenticated-orcid":false,"given":"Adriana Raffin","family":"Pohlmann","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar Tadeu Ferreira","family":"da Costa","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o e Imunologia B\u00e1sica e Aplicada, Universidade Federal do Amazonas, Manaus 69077-000, Brazil"},{"name":"Laborat\u00f3rio de Morfologia Quantitativa, Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Amazonas, Manaus 69077-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Luiz","family":"Boechat","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o e Imunologia B\u00e1sica e Aplicada, Universidade Federal do Amazonas, Manaus 69077-000, Brazil"},{"name":"Laborat\u00f3rio de Terapias Inovadoras, Departamento de Parasitologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Amazonas, Manaus 69077-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.biopha.2018.07.027","article-title":"Novel drug delivery systems for NSAIDs in management of rheumatoid arthritis: An overview","volume":"106","author":"Thakur","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/0002-9343(86)90074-4","article-title":"Effect of diclofenac sodium on the arachidonic acid cascade","volume":"80","author":"Ku","year":"1986","journal-title":"Am. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s40265-015-0392-z","article-title":"Advances in NSAID development: Evolution of diclofenac products using pharmaceutical technology","volume":"75","author":"Altman","year":"2015","journal-title":"Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/ar4174","article-title":"Use of NSAIDs in treating patients with arthritis","volume":"15","author":"Crofford","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/MAJ.0b013e3181ad8cd3","article-title":"Nonsteroidal antiinflammatory drugs and cyclooxygenase inhibition in the gastrointestinal tract: A trip from peptic ulcer to colon cancer","volume":"338","author":"Lanas","year":"2009","journal-title":"Am. J. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.2217\/nnm.15.45","article-title":"Nanomedicine delivers promising treatments for rheumatoid arthritis","volume":"10","author":"Prasad","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_7","first-page":"1245","article-title":"Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages","volume":"8","author":"Yong","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1208\/s12249-013-0048-9","article-title":"Formulation and optimization of nonionic surfactants emulsified nimesulide-loaded PLGA-based nanoparticles by design of experiments","volume":"15","author":"Turk","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.colsurfa.2010.12.011","article-title":"Formulation of lipid core nanocapsules","volume":"375","author":"Venturini","year":"2011","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1111\/j.1476-5381.2009.00244.x","article-title":"Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats","volume":"158","author":"Bernardi","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Keller, K.K., Thomsen, J.S., Stengaard-Pedersen, K., Dagn\u00e6s-Hansen, F., Nyengaard, J.R., and Hauge, E.-M. (2012). Bone formation and resorption are both increased in experimental autoimmune arthritis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0053034"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.5566\/ias.v23.p73-82","article-title":"Stereology and 3D microscopy: Useful alternatives or competitors in the quantitative analysis of microstructures?","volume":"23","author":"Exner","year":"2004","journal-title":"Image Anal. Stereol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1177\/0192623310385140","article-title":"Design-based stereology: Introduction to basic concepts and practical approaches for estimation of cell number","volume":"38","author":"Boyce","year":"2010","journal-title":"Toxicol. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1162\/1535350042973562","article-title":"Quantitative analysis of micro-CT imaging and histopathological signatures of experimental arthritis in rats","volume":"3","author":"Silva","year":"2004","journal-title":"Mol. Imaging."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.joca.2013.05.018","article-title":"Localized 3D analysis of cartilage composition and morphology in small animal models of joint degeneration","volume":"21","author":"Thote","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1166\/jbn.2010.1161","article-title":"Characterization of trans-resveratrol-loaded lipid-core nanocapsules and tissue distribution studies in rats","volume":"6","author":"Frozza","year":"2010","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.neuint.2010.07.012","article-title":"Protective effects of indomethacin-loaded nanocapsules against oxygen-glucose deprivation in organotypic hippocampal slice cultures: Involvement of neuroinflammation","volume":"57","author":"Bernardi","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1166\/jnn.2006.417","article-title":"Physico-chemical characterization and in vivo evaluation of indomethacin ethyl ester-loaded nanocapsules by PCS, TEM, SAXS, interfacial alkaline hydrolysis and antiedematogenic activity","volume":"6","author":"Cruz","year":"2006","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ejpb.2013.04.001","article-title":"In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration","volume":"86","author":"Dallegrave","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/s41565-018-0254-4","article-title":"Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis","volume":"13","author":"Zhang","year":"2018","journal-title":"Nat. Nanotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1186\/s13075-014-0470-8","article-title":"Nociceptive neurons detect cytokines in arthritis","volume":"16","author":"Schaible","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.immuni.2017.02.006","article-title":"Immunopathogenesis of Rheumatoid Arthritis","volume":"46","author":"Firestein","year":"2017","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2094","article-title":"Cytokines in the pathogenesis of rheumatoid arthritis","volume":"7","author":"McInnes","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","first-page":"14","article-title":"New insights into prostaglandin biology","volume":"31","author":"Pelletier","year":"2004","journal-title":"J. Rheumatol."},{"key":"ref_25","first-page":"196","article-title":"Characteristics of human synovial fibroblast activation by IL-1 beta and TNF alpha","volume":"66","author":"Gitter","year":"1989","journal-title":"Immunology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1023\/A:1022350111213","article-title":"The effects of cyclooxygenase 2 inhibitors on cartilage erosion and bone loss in a model of Mycobacterium tuberculosis-induced monoarticular arthritis in the rat","volume":"22","author":"Gilroy","year":"1998","journal-title":"Inflammation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s00011-009-8149-3","article-title":"Combination therapies that inhibit cyclooxygenase-2 and leukotriene synthesis prevent disease in murine collagen induced arthritis","volume":"58","author":"Anderson","year":"2009","journal-title":"Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrrheum.2014.1","article-title":"Persisting eicosanoid pathways in rheumatic diseases","volume":"10","author":"Korotkova","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S274","DOI":"10.1080\/21691401.2018.1491479","article-title":"Effects of human cyclooxygenase-2 gene silencing on synovial cells of rheumatoid arthritis mediated by lentivirus","volume":"46","author":"Leng","year":"2018","journal-title":"Artif Cells Nanomed. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nm1538","article-title":"Dickkopf-1 is a master regulator of joint remodeling","volume":"13","author":"Diarra","year":"2007","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s00210-006-0062-5","article-title":"The comparative study of Sprague-Dawley and Lewis rats in adjuvant-induced arthritis","volume":"373","author":"Cai","year":"2006","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/S0140-6736(07)60784-3","article-title":"New therapies for treatment of rheumatoid arthritis","volume":"370","author":"Smolen","year":"2007","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis","volume":"51","author":"Choy","year":"2012","journal-title":"Rheumatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1365-2559.1994.tb01354.x","article-title":"Stereological analysis of the synovial membrane in rheumatic disorders: Diagnostic value of volume-weighted mean nuclear volume estimation","volume":"25","year":"1994","journal-title":"Histopathology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1600-0714.2007.00630.x","article-title":"Quantitative histological changes of repeated antigen-induced arthritis in the temporomandibular joints of rabbits treated with intra-articular corticosteroid","volume":"37","author":"Kristensen","year":"2008","journal-title":"J. Oral Pathol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/wnan.1334","article-title":"Improving drug biological effects by encapsulation into polymeric nanocapsules","volume":"7","author":"Frank","year":"2015","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1007\/s10637-013-0016-y","article-title":"Ketoprofen-loaded polymeric nanocapsules selectively inhibit cancer cell growth in vitro and in preclinical model of glioblastoma multiforme","volume":"31","author":"Chassot","year":"2013","journal-title":"Investig. New Drugs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejps.2009.11.004","article-title":"Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs","volume":"39","author":"Cattani","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13075-015-0554-0","article-title":"Relative benefit-risk comparing diclofenac to other traditional non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with osteoarthritis or rheumatoid arthritis: A network meta-analysis","volume":"17","author":"Pandhi","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/BF01037953","article-title":"Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis","volume":"25","author":"Fowler","year":"1983","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_42","first-page":"179","article-title":"A pharmacokinetic study of diclofenac sodium in rats","volume":"7","author":"Yuan","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_43","first-page":"527","article-title":"Pharmacokinetics of diclofenac sodium and papaverine hydrochloride after oral administration of tablets to rabbits","volume":"72","author":"Kasperek","year":"2015","journal-title":"Acta Pol. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1111\/jphp.13105","article-title":"Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging","volume":"71","author":"Hellms","year":"2019","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_45","first-page":"229","article-title":"Gastro-intestinal tolerance following oral administration of spray-dried diclofenac-loaded nanocapsules and nanospheres","volume":"11","author":"Guterres","year":"2001","journal-title":"Pharma Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1080\/02652040410001729278","article-title":"Nanoparticle-coated microparticles: Preparation and characterization","volume":"21","author":"Beck","year":"2004","journal-title":"J. Microencapsul."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1039\/C2SM26959G","article-title":"An algorithm to determine the mechanism of drug distribution in lipid-core nanocapsule formulations","volume":"9","author":"Oliveira","year":"2013","journal-title":"Soft Matter"},{"key":"ref_48","first-page":"6603","article-title":"Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model","volume":"10","author":"Boechat","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1365-2818.1986.tb04282.x","article-title":"Estimation of surface area from vertical sections","volume":"142","author":"Baddeley","year":"1986","journal-title":"J. Microsc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1365-2818.1987.tb02837.x","article-title":"The efficiency of systematic sampling in stereology and its prediction","volume":"147","author":"Gundersen","year":"1987","journal-title":"J. Microsc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1006\/jsbi.1996.0013","article-title":"Computer visualization of three-dimensional image data using IMOD","volume":"116","author":"Kremer","year":"1996","journal-title":"J. Struct Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Howard, V., and Reed, M. (2004). Unbiased Stereology: Three-Dimensional Measurement in Microscopy, Garland Science. [2nd ed.].","DOI":"10.4324\/9780203006399"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1046\/j.1365-2818.1999.00460.x","article-title":"Precision of Cavalieri sections and slices with local errors","volume":"193","year":"1999","journal-title":"J. Microsc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5219\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:06:32Z","timestamp":1760126792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,5]]},"references-count":53,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["molecules28135219"],"URL":"https:\/\/doi.org\/10.3390\/molecules28135219","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,5]]}}}