{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:02:31Z","timestamp":1790859751151,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Liposomal drug-delivery systems can improve the formulation performance of poorly soluble compounds by enhancing aqueous dispersion, protecting encapsulated agents, and modifying release behavior. Co-encapsulation of pharmacologically distinct compounds may provide a formulation strategy for comparing combined delivery with a single agent nanoliposomal system. This study aimed to develop and characterize atorvastatin\u2013rutin co-loaded nanoliposomes and to compare their antioxidant, anti-inflammatory, and SRB-based cytotoxic activity with the corresponding free-drug and single-loaded nanoliposomal formulations. Nanoliposomes were prepared by thin-film hydration and characterized by particle size, polydispersity index, zeta potential, encapsulation efficiency, lyophilization-associated retention of encapsulation efficiency, morphology, and in vitro release. A reverse-phase HPLC method was validated for simultaneous atorvastatin and rutin quantification, and lyophilized formulations were evaluated for retention of encapsulation efficiency. In vitro assays included DPPH radical scavenging, nitrite inhibition in LPS-stimulated RAW 264.7 macrophages, and SRB-based cytotoxicity screening across human cancer cell lines and normal periodontal ligament fibroblasts. The co-loaded nanoliposomes achieved encapsulation efficiencies of 88.46% for atorvastatin and 81.74% for rutin; after lyophilization, encapsulation efficiency decreased to 72.31% for atorvastatin and 76.63% for rutin. The nanoliposomal formulations showed measurable DPPH radical-scavenging activity, nitrite-inhibition activity in LPS-stimulated macrophages, and SRB-based antiproliferative activity in several cancer cell lines, while showing no detectable cytotoxicity toward PDL fibroblasts within the tested concentration range. With exquisite similarity to apoptogenic Anti-VEGF antiangiogenesis chemotherapeutic efficacies ofcisplatin; nanoliposomal atorvastatin and co-loaded atorvastatin with rutin were remarkably comparable (in descending order of human VEGF mitigations) in mammary T47D&gt; uterine cervix HeLa&gt; lung A549 adherent monolayers post 72 h incubations. These findings support further investigation of atorvastatin\u2013rutin co-loaded nanoliposomes as an in vitro formulation platform; however, formal synergy analysis, cellular uptake studies, mechanistic assays, pharmacokinetic evaluation, and in vivo safety testing remain necessary. Further in vivo studies are required to determine pharmacokinetic behavior, tissue distribution, therapeutic relevance, and systemic safety.<\/jats:p>","DOI":"10.3390\/ijms27188216","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:33:42Z","timestamp":1789479222000},"page":"8216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and In Vitro Evaluation of Atorvastatin and Rutin Co-Loaded Nanoliposomes for Enhanced Anti-Inflammatory and Cytotoxic Efficacy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0093-2310","authenticated-orcid":false,"given":"Ali","family":"Al-Samydai","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-0193","authenticated-orcid":false,"given":"Violet","family":"Kasabri","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2189-0474","authenticated-orcid":false,"given":"Hanan","family":"Azzam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5759-3538","authenticated-orcid":false,"given":"Maha N.","family":"Abu Hajleh","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Science, Pharmacological and Diagnostic Research Centre, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4840-0460","authenticated-orcid":false,"given":"Said","family":"Moshawih","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdi","family":"Al Nsairat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2635-3619","authenticated-orcid":false,"given":"Lidia","family":"Al-Halaseh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak 61710, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Banat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6088-5675","authenticated-orcid":false,"given":"Zahraa","family":"Al-Zubaidy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain","family":"Al-Tarawneh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Al-Hiari","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaqif","family":"El Khassawna","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Justus Liebig University, Giessen 35390, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3185-647X","authenticated-orcid":false,"given":"Rana","family":"Elstaty","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Abu AlSaman","sequence":"additional","affiliation":[{"name":"Institute of Pancreatic Disease, Department of Gastroenterology, Semmelweis University, \u00dcll\u0151i\u00fat 26, Budapest 1085, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0985-7217","authenticated-orcid":false,"given":"Emad A. S.","family":"Al-Dujaili","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH8 9YL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117429","DOI":"10.1016\/j.biopha.2024.117429","article-title":"Therapeutic efficiency of Tamoxifen\/Orlistat nanocrystals against solid ehrlich carcinoma via targeting TXNIP\/HIF1-\u03b1\/MMP-9\/P27 and BAX\/Bcl2\/P53 signaling pathways","volume":"180","author":"Oriquat","year":"2024","journal-title":"Biomed. 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