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This study aimed to develop liposomal formulations for co\u2010delivery of empagliflozin and rutin, evaluating their anticancer and antioxidant efficacy. PEGylated empagliflozin\u2010loaded nanoliposomes (Empa\u2010NLs) and empagliflozin\u2010rutin co\u2010loaded nanoliposomes (Empa\u2010Rut NLs) were synthesized using the thin\u2010film hydration technique. The formulations were characterized for particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency, and stability. Antiproliferative activity was assessed through MTT assay, and inflammatory and oxidative stress markers were evaluated using ELISA. Empa\u2010NLs had a size of 118.9\u2009\u00b1\u20090.97\u2009nm, zeta potential of \u20130.135\u2009\u00b1\u20090.74mV, and PDI of 0.198\u2009\u00b1\u20090.11, while Empa\u2010Rut NLs measured 133.4\u2009\u00b1\u20091.01\u2009nm, zeta potential of \u20138.78\u2009\u00b1\u20090.85\u2009mV, and PDI of 0.13\u2009\u00b1\u20090.01, with significant differences (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.01). Encapsulation efficiency was 10.8\u2009\u00b1\u20090.103% for empagliflozin and 66.92\u2009\u00b1\u20090.05% for rutin. Both drugs displayed a biphasic release profile. Free empagliflozin showed stronger antiproliferative activity at lower concentrations, while Empa\u2010Rut NLs were more effective at higher concentrations. Empa\u2010NLs upregulated IL\u20101\u03b2 and downregulated catalase, while Empa\u2010Rut NLs and rutin reduced IL\u20101\u03b2 and increased catalase. VEGF levels were elevated with empagliflozin but decreased in the presence of rutin and Empa\u2010Rut NLs. Co\u2010loading empagliflozin and rutin in nanoliposomes enhanced anticancer efficacy and modulated inflammatory and oxidative stress responses, suggesting that this combined drug delivery system may improve cancer therapy outcomes.<\/jats:p>","DOI":"10.1002\/ddr.70155","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T10:55:49Z","timestamp":1757328949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Co\u2010Loaded Nanoparticles of Empagliflozin and Rutin for Pancreatitis Prevention and Anticancer Activity"],"prefix":"10.1002","volume":"86","author":[{"given":"Olla","family":"Maan","sequence":"first","affiliation":[{"name":"Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy Al\u2010Ahliyya Amman University Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Al\u2010Samydai","sequence":"additional","affiliation":[{"name":"Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy Al\u2010Ahliyya Amman University Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-2441","authenticated-orcid":false,"given":"Moath","family":"Alqaraleh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Science Al\u2010Balqa Applied University Al\u2010Salt Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-5879","authenticated-orcid":false,"given":"Hamdi","family":"Nsairat","sequence":"additional","affiliation":[{"name":"Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy Al\u2010Ahliyya Amman University Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Alsanabrah","sequence":"additional","affiliation":[{"name":"Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy Al\u2010Ahliyya Amman University Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1750-6684","authenticated-orcid":false,"given":"Oriana","family":"Awwad","sequence":"additional","affiliation":[{"name":"School of Pharmacy The University of Jordan Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Al\u2010Hiari","sequence":"additional","affiliation":[{"name":"School of Pharmacy The University of Jordan Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.34172\/apb.2023.009"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/znc-2021-0018"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.201900388"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2023-0351"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202301167"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14091771"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcab.2024.103329"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-024-03984-2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-024-03724-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17267"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13113995"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2024.2344182"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14235170"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12668-022-00941-x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2020.1762669"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.18433\/j3sc7j"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158064"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11071867"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-013-0042-y"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.2c00033"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.5101\/nbe.v14i1.p23-37"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics10020057"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","unstructured":"Danpanichkul P. 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