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Niosomal drug delivery systems, known for their controlled release profiles and other advantageous features, can enhance the efficacy of antimicrobial ability of loaded agents. This study aims to propose a novel drug delivery system for combating staphylococcal resistance challenge through examining the antibacterial and antibiofilm properties of myrtenol\u2010loaded niosomal system against MRSA isolates. The niosomal formulation was prepared using the thin\u2010film hydration process, and its physicochemical characteristics were assessed through entrapment efficiency (EE %), in vitro release profile, field\u2010emission scanning electron microscopy (FE\u2010SEM), and dynamic light scattering (DLS). In addition, minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were measured and compared with free myrtenol to evaluate the anti\u2010MRSA activity of the formulated niosomal myrtenol. Furthermore, the effectiveness of niosome containing myrtenol against MRSA biofilms was investigated by examining biofilm minimum inhibitory and eradication concentrations (BMIC\/BMEC). Additionally, the cytotoxicity of synthesized niosomes was assessed on the human foreskin fibroblast cell line (HFF). Results from FE\u2010SEM showed that myrtenol\u2010loaded niosomes were spherical with a diameter of 122.1\u2009nm, while the hydrodynamic size reported from DLS was 130.8\u2009nm. The surface charge and EE% of the prepared niosomal formulation were \u221253.6\u2009mV and 62.90%, respectively. The niosomal myrtenol formulation demonstrated the increased antibacterial activity in comparison with free myrtenol formulation. Furthermore, myrtenol\u2010loaded niosomes reduced the biofilm formation potential in all MRSA isolates and effectively eradicated bacterial biofilms at equivalent concentrations of the non\u2010niosomal formulation. According to this study, niosomes exhibit high potential for drug delivery due to several favorable characteristics, including a sustained\u2010release profile, nontoxicity, small size, and high EE%. Niosomal delivery system presents a novel approach to combat bacterial infections, particularly those caused by MRSA isolates by enhancing antibacterial and antibiofilm activities of free myrtenol.\n                  <\/jats:p>","DOI":"10.1155\/cjid\/2742569","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T02:20:09Z","timestamp":1756952409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Inhibitory Effect of Niosome Containing Myrtenol as an Innovative Approach to Combat Methicillin\u2010Resistant\n                    <i>Staphylococcus aureus<\/i>\n                    (MRSA)"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3539-2238","authenticated-orcid":false,"given":"Jaber","family":"Hemmati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6413-8752","authenticated-orcid":false,"given":"Mohsen","family":"Chiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4038-9618","authenticated-orcid":false,"given":"Babak","family":"Asghari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-9125","authenticated-orcid":false,"given":"Ghodratollah","family":"Roshanaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1518-3308","authenticated-orcid":false,"given":"Sara Soleimani","family":"Asl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6166-5028","authenticated-orcid":false,"given":"Morvarid","family":"Shafiei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-8193","authenticated-orcid":false,"given":"Mohammad Reza","family":"Arabestani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12913-015-0917-x"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2021.1878688"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/714134"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2020.0001"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-023-00811-6"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.589640"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695x.2012.00960.x"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.microb.2025.100281"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1444781"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.2147\/idr.s428103"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2017.11.028"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/scipharm90030039"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/574673"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/gels11040230"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12030264"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/5298565"},{"key":"e_1_2_13_17_2","first-page":"829","article-title":"Niosomes: Revolutionizing the Field of Targeted Drug Delivery System","volume":"8","author":"Bhavsar D.","year":"2023","journal-title":"International Journal of Nephrology and Renovascular Disease"},{"key":"e_1_2_13_18_2","first-page":"1","article-title":"Niosomes as a Targeted Drug Delivery System in the Treatment of Breast Cancer: Preparation, Classification and Mechanisms of Cellular Uptake","author":"Ur R. 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