{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:40:13Z","timestamp":1774276813393,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T00:00:00Z","timestamp":1434412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX) and superparamagnetic iron oxide nanoparticles (SPIONs) were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than \u221216 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM) photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 \u03bcg\/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications.<\/jats:p>","DOI":"10.3390\/molecules200611103","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T10:28:09Z","timestamp":1434450489000},"page":"11103-11118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Solid Lipid Nanoparticles: A Potential Multifunctional Approach towards Rheumatoid Arthritis Theranostics"],"prefix":"10.3390","volume":"20","author":[{"given":"Jo\u00e3o","family":"Albuquerque","sequence":"first","affiliation":[{"name":"UCIBIO, ICETA REQUIMTE, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Catarina","family":"Moura","sequence":"additional","affiliation":[{"name":"UCIBIO, ICETA REQUIMTE, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Bruno","family":"Sarmento","sequence":"additional","affiliation":[{"name":"Biocarrier Group, INEB\u2014Instituto de Engenharia Biom\u00e9dica, Rua do Campo Alegre, 823,  4150-180 Porto, Portugal"},{"name":"CESPU, Instituto de Investiga\u00e7\u00e3o e Forma\u00e7\u00e3o Avan\u00e7ada em Ci\u00eancias e Tecnologias da Sa\u00fade,  Rua Central de Gandra, 1317, 4585-116 Granda PRD, Portugal"}]},{"given":"Salette","family":"Reis","sequence":"additional","affiliation":[{"name":"UCIBIO, ICETA REQUIMTE, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1136\/ard.2009.123919","article-title":"Treating rheumatoid arthritis to target: Recommendations of an international task force","volume":"69","author":"Smolen","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nrrheum.2013.8","article-title":"The problem of choice: Current biologic agents and future prospects in RA","volume":"9","author":"Choy","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.amjmed.2007.04.005","article-title":"Rheumatoid arthritis: Diagnosis and management","volume":"120","author":"Majithia","year":"2007","journal-title":"Am. J. Med."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1148\/rg.301095089","article-title":"MR imaging of early rheumatoid arthritis","volume":"30","year":"2010","journal-title":"RadioGraphics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1109\/TNB.2008.2011864","article-title":"Development of superparamagnetic iron oxide nanoparticles (SPIONS) for translation to clinical applications","volume":"7","author":"Lin","year":"2008","journal-title":"IEEE Trans. Nanobiosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1136\/ard.60.8.729","article-title":"Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis","volume":"60","author":"Cutolo","year":"2001","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","first-page":"4911","article-title":"Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application","volume":"9","author":"Moura","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.3390\/ijms14024242","article-title":"Lipid nanotechnology","volume":"14","author":"Mashaghi","year":"2013","journal-title":"Int. J Mol. Sci."},{"key":"ref_10","first-page":"WMC002867","article-title":"Nanotechnology and its applications in drug delivery: A review","volume":"3","author":"Sehgal","year":"2013","journal-title":"Int. J. Med. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ijpharm.2012.07.017","article-title":"Drug delivery to inflamed colon by nanoparticles: Comparison of different strategies","volume":"440","author":"Coco","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.addr.2012.04.010","article-title":"Nanoparticles in drug delivery: Past, present and future","volume":"65","author":"Couvreur","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1007\/s11095-013-1290-2","article-title":"Novel nanostructured lipid carrier co-loaded with doxorubicin and docosahexaenoic acid demonstrates enhanced in vitro activity and overcomes drug resistance in MCF-7\/Adr cells","volume":"31","author":"Mussi","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.colsurfb.2012.01.001","article-title":"Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: A novel strategy to avoid intraduodenal administration","volume":"95","author":"Venishetty","year":"2012","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"813","DOI":"10.3109\/1061186X.2012.716845","article-title":"Nanostructured lipid carriers system: Recent advances in drug delivery","volume":"20","author":"Iqbal","year":"2012","journal-title":"J. Drug Target."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sibeko, B., Choonara, Y.E., du Toit, L.C., Modi, G., Naidoo, D., Khan, R.A., Kumar, P., Ndesendo, V.M., Iyuke, S.E., and Pillay, V. (2012). Composite polylactic-methacrylic Acid copolymer nanoparticles for the delivery of methotrexate. J. Drug Deliv.","DOI":"10.1155\/2012\/579629"},{"key":"ref_17","first-page":"3333","article-title":"Solid lipid nanoparticles modified with stearic acid-octaarginine for oral administration of insulin","volume":"7","author":"Zhang","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_18","first-page":"196","article-title":"Lipid shell modified with combination of lipid and phospholipids in solid lipid nanoparticles for engineered specificity of paclitaxel in tumor bearing mice","volume":"5","author":"Patil","year":"2013","journal-title":"Int. J. Drug Deliv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1021\/cr300143v","article-title":"Functionalizing nanoparticles with biological molecules: Developing chemistries that facilitate nanotechnology","volume":"113","author":"Sapsford","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1096\/fj.12-218081","article-title":"Programmable nanoparticle functionalization for in vivo targeting","volume":"27","author":"Pan","year":"2013","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.2147\/IJN.S60674","article-title":"Role of the charge, carbon chain length, and content of surfactant on the skin penetration of meloxicam-loaded liposomes","volume":"9","author":"Duangjit","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1021\/bk-2008-0992.ch008","article-title":"Engineering of solid lipid nanoparticles for biomedical applications","volume":"Volume 992","author":"Parris","year":"2008","journal-title":"New Delivery Systems for Controlled Drug Release from Naturally Occurring Materials"},{"key":"ref_23","first-page":"1333","article-title":"Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles","volume":"368","author":"Sperling","year":"2010","journal-title":"Philos. Trans. Ser. A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0378-5173(01)00882-1","article-title":"Effect of lipid matrix and size of solid lipid nanoparticles (SLN) on the viability and cytokine production of macrophages","volume":"231","author":"Scholer","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijpharm.2012.09.054","article-title":"Brain delivery of camptothecin by means of solid lipid nanoparticles: Formulation design, in vitro and in vivo studies","volume":"439","author":"Martins","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_26","unstructured":"Block, I.A. (2010). Particle Sizing by 3D Cross-correlation DLS in Highly Scattering Samples, LS Instruments."},{"key":"ref_27","first-page":"80","article-title":"Solid lipid nanoparticles: Review","volume":"2","author":"Ekambaram","year":"2012","journal-title":"Sci. Rev. Chem. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1128\/iai.63.5.1698-1702.1995","article-title":"Effect of Polyclonal and Monoclonal antibodies on Surface properties of Streptococcus Sobrinus","volume":"63","author":"Raamsdonk","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S0304-8853(03)00469-4","article-title":"FTIR study of surfactant bonding to FePt nanoparticles","volume":"266","author":"Shukla","year":"2003","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1111\/j.1151-2916.2001.tb00967.x","article-title":"Detection of phase separation by ftir in a liquid-crystal-display substrate aluminoborosilicate glass","volume":"84","author":"Kato","year":"2001","journal-title":"J. Am. Ceram. Soc."},{"key":"ref_31","first-page":"539","article-title":"Solid Lipid Nanoparticles (SLN)\u2014Effects of lipid composition on in vitro degradation and in vivo toxicity","volume":"61","author":"Weyhers","year":"2006","journal-title":"Pharmazie"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1634\/theoncologist.11-6-694","article-title":"Understanding and managing methotrexate nephrotoxicity","volume":"11","author":"Widemann","year":"2006","journal-title":"Oncologist"},{"key":"ref_33","first-page":"77","article-title":"Effets de la temp\u00e9rature et du pH sur la cin\u00e9tique de dissolution du m\u00e9thotrexato en milieu aqueux","volume":"54","author":"Houngbossa","year":"1996","journal-title":"Ann. Pharm. Fr."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/6\/11103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:58Z","timestamp":1760215678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/6\/11103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,16]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6]]}},"alternative-id":["molecules200611103"],"URL":"https:\/\/doi.org\/10.3390\/molecules200611103","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,16]]}}}