{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:05:41Z","timestamp":1791335141242,"version":"4.3.1"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU)","award":["RG-44-166-43"],"award-info":[{"award-number":["RG-44-166-43"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Systemic treatments for rheumatoid arthritis are associated with many side effects. This study aimed to minimize the side effects associated with the systemic administration of leflunomide (LEF) by formulating LEF-loaded emulsomes (EMLs) for intra-articular administration. Additionally, EMLs were loaded with supramagnetic nanoparticles (SPIONs) to enhance joint localization, where a magnet was placed on the joint area after intra-articular administration. Full in vitro characterization, including colloidal characteristics, entrapment efficiency, and in vitro release were conducted besides the in vivo evaluation in rats with adjuvant-induced arthritis. In vivo study included joint diameter measurement, X-ray radiographic analysis, RT-PCR analysis, Western blotting, ELISA for inflammatory markers, and histopathological examination of dissected joints. The particle size and entrapment efficiency of the selected LEF SPION EMLs were 198.2 nm and 83.7%, respectively. The EMLs exhibited sustained release for 24 h. Moreover, in vivo evaluation revealed LEF SPION EMLs to be superior to the LEF suspension, likely due to the increase in LEF solubility by nanoencapsulation that improved the pharmacological effects and the use of SPION that ensured the localization of EMLs in the intra-articular cavity upon administration.<\/jats:p>","DOI":"10.3390\/pharmaceutics14102005","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"2005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Development and Evaluation of Novel Leflunomide SPION Bioemulsomes for the Intra-Articular Treatment of Arthritis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4243-1442","authenticated-orcid":false,"given":"Haidy","family":"Abbas","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6465-3102","authenticated-orcid":false,"given":"Heba A.","family":"Gad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"},{"name":"Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-5118","authenticated-orcid":false,"given":"Nesrine S","family":"El Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila Ahmed","family":"Rashed","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11956, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7072-2389","authenticated-orcid":false,"given":"Mohamed A.","family":"Khattab","sequence":"additional","affiliation":[{"name":"Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Cairo 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad O.","family":"Noor","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-9361","authenticated-orcid":false,"given":"Mariam","family":"Zewail","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.4049\/jimmunol.177.8.5727","article-title":"Interaction of vascular endothelial growth factor 165 with neuropilin-1 protects rheumatoid synoviocytes from apoptotic death by regulating Bcl-2 expression and Bax translocation","volume":"177","author":"Kim","year":"2006","journal-title":"J. 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