{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:36:19Z","timestamp":1792514179901,"version":"4.5.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002386","name":"Cairo University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002386","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) is a major cause of skin and soft tissue infections which, due to the spread of antimicrobial resistance, have become increasingly serious. Bacterial skin infection affects the barrier function of skin causing depletion of the ceramide content in the stratum corneum (SC) of the epidermis. In the study reported herein, luteolin (LUT) a naturally-occurring flavonoid was incorporated in PEGylated cerosomes (PCs) to boost its antibacterial action as a topical application. The opimal formulation of the surface-modified lipidic vesicles was chosen with the aid of a 2<jats:sup>3<\/jats:sup> full factorial design. The effectiveness of the optimal LUT formulation which was developed was evaluated using several MRSA strains both in vitro and in vivo studies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A 2<jats:sup>3<\/jats:sup> full factorial design was employed for the preparation of the optimum PC formulation, designated herein as F5. A comparative in vitro release study revealed the superiority of F5 over a LUT suspension in solubilizing and releasing after 24\u00a0h, a higher percentage 78.1\u2009\u00b1\u20091.8% of luteolin compared with only 18.3\u2009\u00b1\u20092.1% for the luteolin suspension. When tested against MRSA strains, F5 showed antimicrobial activity that was higher than that of the luteolin suspension, having a MIC value of 187.5\u00a0\u00b5g\/mL versus 1500\u00a0\u00b5g\/mL. In addition to having enhanced anti-virulence activity than the luteolin suspension in terms of antibiofilm formation (with % inhibition ranging from 45 to 99% with the tested strains at 0.5\u2009\u00d7\u2009and 0.25\u2009\u00d7\u2009MICs, where the luteolin suspension only had a range from 1 to 45%), enhanced anti-pigment production, and anti-\u03b1-hemolysin activity were also observed. Moreover, F5 affected the cell wall integrity as confirmed by transmission electron microscopy (TEM). Scanning electron microscopy (SEM) verified the effect of F5 on bacterial biofilm formation, showing reduction of cellular adhesion and disruption of biofilm, factors which greatly contribute to bacterial pathogenesis and antibiotic resistance. When compared to the negative control and the luteolin suspension groups, the F5 formulation also resulted in reducing the bacterial load in the murine skin infection model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>F5 PEGylated cerosomes are potential new potent defense agents against MRSA infections, demonstrating promising therapeutic capabilities.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12866-025-03873-0","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T06:56:51Z","timestamp":1743404211000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Luteolin loaded PEGylated cerosomes: a novel treatment for MRSA skin infections"],"prefix":"10.1186","volume":"25","author":[{"given":"Sally A.","family":"Mohamed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa A.","family":"Eraqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paris E.","family":"Georghiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Y.","family":"Zakaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"issue":"11","key":"3873_CR1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/nrmicro.2017.104","volume":"15","author":"B Krismer","year":"2017","unstructured":"Krismer B, et al. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat Rev Microbiol. 2017;15(11):675\u201387.","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"3873_CR2","doi-asserted-by":"publisher","first-page":"e00181","DOI":"10.1128\/cmr.00181-19","volume":"33","author":"DM De Oliveira","year":"2020","unstructured":"De Oliveira DM, et al. Antimicrobial resistance in ESKAPE pathogens. Clin Microbiol Rev. 2020;33(3):e00181-19. https:\/\/doi.org\/10.1128\/cmr.00181-19.","journal-title":"Clin Microbiol Rev"},{"issue":"4","key":"3873_CR3","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41579-018-0147-4","volume":"17","author":"NA Turner","year":"2019","unstructured":"Turner NA, et al. Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nat Rev Microbiol. 2019;17(4):203\u201318.","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"3873_CR4","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/CMR.00134-14","volume":"28","author":"SY Tong","year":"2015","unstructured":"Tong SY, et al. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28(3):603\u201361.","journal-title":"Clin Microbiol Rev"},{"key":"3873_CR5","doi-asserted-by":"crossref","unstructured":"David, M.Z., R.S.J.S.a.m. Daum, pathology, immunology, therapy, and prophylaxis, Treatment of Staphylococcus aureus infections. 2017: p. 325\u2013383.","DOI":"10.1007\/82_2017_42"},{"issue":"11","key":"3873_CR6","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1080\/14760584.2016.1179583","volume":"15","author":"GH Dayan","year":"2016","unstructured":"Dayan GH, et al. Staphylococcus aureus: the current state of disease, pathophysiology and strategies for prevention. Expert Rev Vaccines. 2016;15(11):1373\u201392.","journal-title":"Expert Rev Vaccines"},{"issue":"27","key":"3873_CR7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.5897\/AJMR2017.8742","volume":"12","author":"E Rana","year":"2018","unstructured":"Rana E, et al. Study on prevalence and genetic discrimination of methicillin-resistant Staphylococcus aureus (MRSA) in Egyptian hospitals. African J Microbiol Res. 2018;12(27):629\u201346.","journal-title":"African J Microbiol Res"},{"issue":"6","key":"3873_CR8","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1128\/AAC.44.6.1549-1555.2000","volume":"44","author":"Y Katayama","year":"2000","unstructured":"Katayama Y, et al. A new class of genetic element, Staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 2000;44(6):1549\u201355.","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"3873_CR9","first-page":"46","volume":"11","author":"C Rodr\u00edguez-Melc\u00f3n","year":"2021","unstructured":"Rodr\u00edguez-Melc\u00f3n C, et al. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for twelve antimicrobials (biocides and antibiotics) in eight strains of Listeria monocytogenes. Biology (Basel). 2021;11(1):46.","journal-title":"Biology (Basel)"},{"key":"3873_CR10","doi-asserted-by":"publisher","first-page":"561002","DOI":"10.3389\/fmicb.2020.561002","volume":"11","author":"L Wang","year":"2020","unstructured":"Wang L, et al. Antibacterial activity of Cinnamomum camphora essential oil on Escherichia coli during planktonic growth and biofilm formation. Front Microbiol. 2020;11:561002.","journal-title":"Front Microbiol"},{"key":"3873_CR11","doi-asserted-by":"crossref","unstructured":"Guo, J., et al., Thiazole-based analogs as potential antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) and their SAR elucidation. 2023: p. 115689.","DOI":"10.1016\/j.ejmech.2023.115689"},{"issue":"2","key":"3873_CR12","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3934\/microbiol.2019.2.117","volume":"5","author":"MU Okwu","year":"2019","unstructured":"Okwu MU, et al. Methicillin-resistant Staphylococcus aureus (MRSA) and anti-MRSA activities of extracts of some medicinal plants: a brief review. AIMS Microbiol. 2019;5(2):117.","journal-title":"AIMS Microbiol"},{"issue":"17","key":"3873_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.4103\/0973-7847.156329","volume":"9","author":"AJPR Kali","year":"2015","unstructured":"Kali AJPR. Antibiotics and bioactive natural products in treatment of methicillin resistant Staphylococcus aureus: a brief review. Pharmacogn Rev. 2015;9(17):29.","journal-title":"Pharmacogn Rev"},{"key":"3873_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13756-020-00714-9","volume":"9","author":"A Shariati","year":"2020","unstructured":"Shariati A, et al. The global prevalence of Daptomycin, Tigecycline, Quinupristin\/Dalfopristin, and Linezolid-resistant Staphylococcus aureus and coagulase\u2013negative staphylococci strains: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2020;9:1\u201320.","journal-title":"Antimicrob Resist Infect Control"},{"key":"3873_CR15","doi-asserted-by":"crossref","unstructured":"Pothineni BK, AJANR, Keller. Nanoparticle\u2010Based Formulations of Glycopeptide Antibiotics: A Means for Overcoming Vancomycin Resistance in Bacterial Pathogens? 2023. 3(4): p. 2200134.","DOI":"10.1002\/anbr.202200134"},{"key":"3873_CR16","unstructured":"Control, C.f.D. and Prevention, Antibiotic resistance threats in the United States, 2019. 2019: US Department of Health and Human Services, Centres for Disease Control and\u00a0\u2026."},{"key":"3873_CR17","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jhin.2020.11.010","volume":"107","author":"J Ruiz","year":"2021","unstructured":"Ruiz J. Enhanced antibiotic resistance as a collateral COVID-19 pandemic effect? J Hosp Infect. 2021;107:114.","journal-title":"J Hosp Infect"},{"issue":"4","key":"3873_CR18","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.cmi.2020.12.018","volume":"27","author":"BJ Langford","year":"2021","unstructured":"Langford BJ, et al. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Clin Microbiol Infect. 2021;27(4):520\u201331.","journal-title":"Clin Microbiol Infect"},{"key":"3873_CR19","unstructured":"COVID, C., 19: US impact on antimicrobial resistance, special report 2022. 2022. 2023."},{"key":"3873_CR20","doi-asserted-by":"crossref","unstructured":"Algammal, A., et al., Emerging multidrug-resistant bacterial pathogens \u201csuperbugs\u201d: a rising public health threat. 2023, Frontiers Media SA. p. 1135614.","DOI":"10.3389\/fmicb.2023.1135614"},{"key":"3873_CR21","doi-asserted-by":"publisher","first-page":"846260","DOI":"10.3389\/fepid.2022.846260","volume":"2","author":"PG Goldschmidt","year":"2022","unstructured":"Goldschmidt PG. The global health security index: another look. Front Epidemiol. 2022;2:846260.","journal-title":"Front Epidemiol"},{"key":"3873_CR22","first-page":"102492","volume":"115","author":"T Cernev","year":"2020","unstructured":"Cernev T, Fenner RJF. The importance of achieving foundational sustainable development goals in reducing global risk. Lancet Public Health. 2020;115:102492.","journal-title":"Lancet Public Health"},{"issue":"11","key":"3873_CR23","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1080\/14740338.2021.1928633","volume":"20","author":"P Chandra","year":"2021","unstructured":"Chandra P, et al. Antimicrobial resistance and the post antibiotic era: better late than never effort. Expert Opin Drug Saf. 2021;20(11):1375\u201390.","journal-title":"Expert Opin Drug Saf"},{"key":"3873_CR24","doi-asserted-by":"publisher","first-page":"449147","DOI":"10.3389\/fmicb.2019.01404","volume":"10","author":"JV Pham","year":"2019","unstructured":"Pham JV, et al. A review of the microbial production of bioactive natural products and biologics. Front Microbiol. 2019;10:449147.","journal-title":"Front Microbiol"},{"issue":"6","key":"3873_CR25","doi-asserted-by":"publisher","first-page":"e04085","DOI":"10.1016\/j.heliyon.2020.e04085","volume":"6","author":"GT El-Bassyouni","year":"2020","unstructured":"El-Bassyouni GT, et al. Hydroxyapatite nanoparticles derived from mussel shells for in vitro cytotoxicity test and cell viability. Heliyon. 2020;6(6):e04085.","journal-title":"Heliyon"},{"issue":"1","key":"3873_CR26","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s00289-022-04091-8","volume":"80","author":"M Azeem","year":"2023","unstructured":"Azeem M, et al. An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: a review. Polym Bull (Berl). 2023;80(1):241\u201362.","journal-title":"Polym Bull (Berl)"},{"issue":"10","key":"3873_CR27","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1111\/bph.14987","volume":"177","author":"T Boeing","year":"2020","unstructured":"Boeing T, et al. Luteolin prevents irinotecan-induced intestinal mucositis in mice through antioxidant and anti-inflammatory properties. Br J Pharmacol. 2020;177(10):2393\u2013408.","journal-title":"Br J Pharmacol"},{"issue":"6","key":"3873_CR28","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.3390\/nu14061155","volume":"14","author":"S Caporali","year":"2022","unstructured":"Caporali S, et al. Anti-inflammatory and active biological properties of the plant-derived bioactive compounds luteolin and luteolin 7-glucoside. Nutrients. 2022;14(6):1155.","journal-title":"Nutrients"},{"issue":"4","key":"3873_CR29","doi-asserted-by":"publisher","first-page":"130","DOI":"10.3390\/pharmacy11040130","volume":"11","author":"M Spanakis","year":"2023","unstructured":"Spanakis M, et al. Antibiotics and lipid-modifying agents: potential drug-drug interactions and their clinical implications. Pharmacy (Basel). 2023;11(4):130.","journal-title":"Pharmacy (Basel)"},{"issue":"1","key":"3873_CR30","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.jaad.2014.01.891","volume":"71","author":"MH Meckfessel","year":"2014","unstructured":"Meckfessel MH, Brandt S. The structure, function, and importance of ceramides in skin and their use as therapeutic agents in skin-care products. J American Acad Dermatol. 2014;71(1):177\u201384.","journal-title":"J American Acad Dermatol"},{"key":"3873_CR31","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.2147\/IJN.S443812","volume":"19","author":"SF Elhabal","year":"2024","unstructured":"Elhabal SF, et al. Revolutionizing psoriasis topical treatment: enhanced efficacy through ceramide\/phospholipid composite cerosomes co-delivery of cyclosporine and dithranol: in vitro, ex vivo, and in vivo studies. Int J Nanomed. 2024;19:1163\u201387.","journal-title":"Int J Nanomed"},{"key":"3873_CR32","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.colsurfb.2013.04.045","volume":"110","author":"E Vega","year":"2013","unstructured":"Vega E, et al. Flurbiprofen PLGA-PEG nanospheres: Role of hydroxy-\u03b2-cyclodextrin on ex vivo human skin permeation and in vivo topical anti-inflammatory efficacy. Colloids Surf B Biointerfaces. 2013;110:339\u201346.","journal-title":"Colloids Surf B Biointerfaces"},{"key":"3873_CR33","doi-asserted-by":"crossref","unstructured":"Albash R, et al. Tailoring of PEGylated bilosomes for promoting the transdermal delivery of olmesartan medoxomil: in-vitro characterization, ex-vivo permeation and in-vivo assessment. 2019: p. 6555\u20136574.","DOI":"10.2147\/IJN.S213613"},{"issue":"1","key":"3873_CR34","doi-asserted-by":"publisher","first-page":"2202357","DOI":"10.1080\/14756366.2023.2202357","volume":"38","author":"AA Al-Karmalawy","year":"2023","unstructured":"Al-Karmalawy AA, et al. Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N-(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies. J Enzyme Inhib Med Chem. 2023;38(1):2202357.","journal-title":"J Enzyme Inhib Med Chem"},{"issue":"1","key":"3873_CR35","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1021\/acsomega.1c05628","volume":"7","author":"SS Imam","year":"2021","unstructured":"Imam SS, et al. Formulation and evaluation of luteolin-loaded nanovesicles: In vitro physicochemical characterization and viability assessment. ACS Omega. 2021;7(1):1048\u201356.","journal-title":"ACS Omega"},{"key":"3873_CR36","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s40199-020-00355-8","volume":"28","author":"SM Abd El-Halim","year":"2020","unstructured":"Abd El-Halim SM, et al. Stabilized oral nanostructured lipid carriers of Adefovir Dipivoxil as a potential liver targeting: Estimation of liver function panel and uptake following intravenous injection of radioiodinated indicator. Daru. 2020;28:517\u201332.","journal-title":"Daru"},{"issue":"2","key":"3873_CR37","doi-asserted-by":"publisher","first-page":"606","DOI":"10.3390\/pharmaceutics15020606","volume":"15","author":"MM Mostafa","year":"2023","unstructured":"Mostafa MM, et al. Chitosan surface-modified PLGA nanoparticles loaded with cranberry powder extract as a potential oral delivery platform for targeting colon cancer cells. Pharmaceutics. 2023;15(2):606.","journal-title":"Pharmaceutics"},{"key":"3873_CR38","doi-asserted-by":"publisher","first-page":"122980","DOI":"10.1016\/j.ijpharm.2023.122980","volume":"640","author":"AA Elmaaty","year":"2023","unstructured":"Elmaaty AA, et al. Experimental design of D-\u03b1-tocopherol polyethylene glycol 1000 succinate stabilized bile salt based Nano-vesicles for improved cytotoxicity and bioavailability of colchicine binding site inhibitor Candidates: In Vitro, in silico, and pharmacokinetic studies. Int J Pharm. 2023;640:122980.","journal-title":"Int J Pharm"},{"key":"3873_CR39","doi-asserted-by":"publisher","first-page":"123385","DOI":"10.1016\/j.ijpharm.2023.123385","volume":"646","author":"MY Zakaria","year":"2023","unstructured":"Zakaria MY, et al. Investigating the superiority of chitosan\/D-alpha-tocopheryl polyethylene glycol succinate binary coated bilosomes in promoting the cellular uptake and anti-SARS-CoV-2 activity of polyphenolic herbal drug candidate. Int J Pharm. 2023;646:123385.","journal-title":"Int J Pharm"},{"key":"3873_CR40","doi-asserted-by":"publisher","first-page":"104775","DOI":"10.1016\/j.jddst.2023.104775","volume":"87","author":"RE Elnady","year":"2023","unstructured":"Elnady RE, et al. Phytomedicinal flavonoid loaded phospholipid sheathed lipidic nano-carriers as a platform with boosted oral anti-mycobacterium activity. J Drug Deliv Sci Technol. 2023;87:104775.","journal-title":"J Drug Deliv Sci Technol"},{"key":"3873_CR41","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.2147\/IDR.S296000","volume":"14","author":"HTN El-Din","year":"2021","unstructured":"El-Din HTN, et al. Phenotype-genotype characterization and antibiotic-resistance correlations among colonizing and infectious methicillin-resistant Staphylococcus aureus recovered from intensive care units. Infect Drug Resist. 2021;14:1557.","journal-title":"Infect Drug Resist"},{"key":"3873_CR42","doi-asserted-by":"crossref","unstructured":"Zakaria MY, WA Eraqi, SAJIJoP. Mohamed, Ultra-deformable free fatty acid based nano-carriers for topical delivery of Luteolin: A Potential Paradigm for management of Methicillin-Resistant Staphylococcus aureus skin infections. 2023: p. 123259.","DOI":"10.1016\/j.ijpharm.2023.123259"},{"issue":"4","key":"3873_CR43","doi-asserted-by":"publisher","first-page":"e01934","DOI":"10.1128\/JCM.01934-17","volume":"56","author":"RM Humphries","year":"2018","unstructured":"Humphries RM, et al. CLSI methods development and standardization working group best practices for evaluation of antimicrobial susceptibility tests. J Clin Microbiol. 2018;56(4):e01934-17.","journal-title":"J Clin Microbiol"},{"issue":"2","key":"3873_CR44","doi-asserted-by":"publisher","first-page":"435","DOI":"10.3390\/molecules27020435","volume":"27","author":"L Zhang","year":"2022","unstructured":"Zhang L, et al. The untargeted phytochemical profile of three meliaceae species related to in vitro cytotoxicity and anti-virulence activity against mrsa isolates. Molecules. 2022;27(2):435.","journal-title":"Molecules"},{"key":"3873_CR45","doi-asserted-by":"crossref","unstructured":"Weigel D, JJCSHP Glazebrook, Transmission electron microscopy (TEM) freeze substitution of plant tissues. 2010. 2010(7): p. pdb. prot4959.","DOI":"10.1101\/pdb.prot4959"},{"key":"3873_CR46","doi-asserted-by":"publisher","first-page":"114204","DOI":"10.1016\/j.ejmech.2022.114204","volume":"234","author":"MM Elsebaie","year":"2022","unstructured":"Elsebaie MM, et al. Exploring the structure-activity relationships of diphenylurea as an antibacterial scaffold active against methicillin-and vancomycin-resistant Staphylococcus aureus. Eur J Med Chem. 2022;234:114204.","journal-title":"Eur J Med Chem"},{"key":"3873_CR47","doi-asserted-by":"publisher","first-page":"122274","DOI":"10.1016\/j.ijpharm.2022.122274","volume":"628","author":"P Deng","year":"2022","unstructured":"Deng P, et al. Employment of PEGylated ultra-deformable transferosomes for transdermal delivery of tapentadol with boosted bioavailability and analgesic activity in post-surgical pain. Int J Pharm. 2022;628:122274.","journal-title":"Int J Pharm"},{"issue":"1","key":"3873_CR48","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1080\/10717544.2022.2126028","volume":"29","author":"MY Zakaria","year":"2022","unstructured":"Zakaria MY, et al. Boosting the anti MERS-CoV activity and oral bioavailability of resveratrol via PEG-stabilized emulsomal nano-carrier: factorial design, in-vitro and in-vivo assessments. Drug Deliv. 2022;29(1):3155\u201367.","journal-title":"Drug Deliv"},{"issue":"1","key":"3873_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10717544.2020.1859000","volume":"28","author":"R Albash","year":"2021","unstructured":"Albash R, et al. Utilization of PEGylated cerosomes for effective topical delivery of fenticonazole nitrate: in-vitro characterization, statistical optimization, and in-vivo assessment. Drug Deliv. 2021;28(1):1\u20139.","journal-title":"Drug Deliv"},{"issue":"1","key":"3873_CR50","doi-asserted-by":"publisher","first-page":"2162157","DOI":"10.1080\/10717544.2022.2162157","volume":"30","author":"MY Zakaria","year":"2023","unstructured":"Zakaria MY, et al. Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity\u2019: in-vitro and insilico studies. Drug Deliv. 2023;30(1):2162157.","journal-title":"Drug Deliv"},{"key":"3873_CR51","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jconrel.2016.12.022","volume":"247","author":"M Roberts","year":"2017","unstructured":"Roberts M, et al. Topical and cutaneous delivery using nanosystems. J Control Release. 2017;247:86\u2013105.","journal-title":"J Control Release"},{"key":"3873_CR52","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.plipres.2014.01.004","volume":"54","author":"BM Castro","year":"2014","unstructured":"Castro BM, Prieto M, Silva LC. Ceramide: a simple sphingolipid with unique biophysical properties. Progress Lipid Res. 2014;54:53\u201367.","journal-title":"Progress Lipid Res"},{"issue":"1","key":"3873_CR53","doi-asserted-by":"publisher","first-page":"2679","DOI":"10.1080\/14756366.2022.2116016","volume":"37","author":"I Zaki","year":"2022","unstructured":"Zaki I, et al. Design and synthesis of new trimethoxylphenyl-linked combretastatin analogues loaded on diamond nanoparticles as a panel for ameliorated solubility and antiproliferative activity. J Enzyme Inhib Med Chem. 2022;37(1):2679\u2013701.","journal-title":"J Enzyme Inhib Med Chem"},{"key":"3873_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1208\/s12249-021-01924-z","volume":"22","author":"S Mosallam","year":"2021","unstructured":"Mosallam S, et al. Fabrication of highly deformable bilosomes for enhancing the topical delivery of terconazole: in vitro characterization, microbiological evaluation, and in vivo skin deposition study. AAPS PharmSciTech. 2021;22:1\u201312.","journal-title":"AAPS PharmSciTech"},{"issue":"10","key":"3873_CR55","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.3390\/nano9101365","volume":"9","author":"C Aur\u00eda-Soro","year":"2019","unstructured":"Aur\u00eda-Soro C, et al. Interactions of nanoparticles and biosystems: microenvironment of nanoparticles and biomolecules in nanomedicine. Nanomaterials (Basel). 2019;9(10):1365.","journal-title":"Nanomaterials (Basel)"},{"issue":"1","key":"3873_CR56","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jconrel.2006.11.028","volume":"118","author":"Y Hu","year":"2007","unstructured":"Hu Y, et al. Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells. J Control Release. 2007;118(1):7\u201317.","journal-title":"J Control Release"},{"key":"3873_CR57","doi-asserted-by":"publisher","first-page":"121717","DOI":"10.1016\/j.ijpharm.2022.121717","volume":"619","author":"H Hegazy","year":"2022","unstructured":"Hegazy H, et al. TPGS surface modified bilosomes as boosting cytotoxic oral delivery systems of curcumin against doxorubicin resistant MCF-7 breast cancer cells. Int J Pharm. 2022;619:121717.","journal-title":"Int J Pharm"},{"key":"3873_CR58","doi-asserted-by":"crossref","unstructured":"Affi W, et al., Comparative study of phenolic compound antioxidant and antimicrobial activities of fruits peel and cladodes from tunisian opuntia stricta. J Altern Complement Integr Med 7: 201. 2021. 6: p. 2.","DOI":"10.24966\/ACIM-7562\/100202"},{"key":"3873_CR59","doi-asserted-by":"publisher","first-page":"102105","DOI":"10.1016\/j.bcab.2021.102105","volume":"35","author":"CE Aruwa","year":"2021","unstructured":"Aruwa CE, et al. Enzymatic dimerization of luteolin enhances antioxidant and antimicrobial activities. Biocatalysis Agricult Biotechnol. 2021;35:102105.","journal-title":"Biocatalysis Agricult Biotechnol"},{"key":"3873_CR60","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.2147\/IDR.S253363","volume":"13","author":"Y Guo","year":"2020","unstructured":"Guo Y, et al. The antibacterial activity and mechanism of action of luteolin against Trueperella pyogenes. Infect Drug Resist. 2020;13:1697\u2013711.","journal-title":"Infect Drug Resist"},{"key":"3873_CR61","doi-asserted-by":"publisher","first-page":"104056","DOI":"10.1016\/j.micpath.2020.104056","volume":"142","author":"W Qian","year":"2020","unstructured":"Qian W, et al. Antimicrobial mechanism of luteolin against Staphylococcus aureus and Listeria monocytogenes and its antibiofilm properties. Microb Pathog. 2020;142:104056.","journal-title":"Microb Pathog"},{"key":"3873_CR62","doi-asserted-by":"crossref","unstructured":"Algammal AM, et al., Methicillin-Resistant Staphylococcus aureus (MRSA): one health perspective approach to the bacterium epidemiology, virulence factors, antibiotic-resistance, and zoonotic impact. 2020: p. 3255\u20133265.","DOI":"10.2147\/IDR.S272733"},{"key":"3873_CR63","doi-asserted-by":"crossref","unstructured":"Sun Y, et al. Luteolin inhibits the biofilm formation and cytotoxicity of methicillin-resistant Staphylococcus aureus via decreasing bacterial toxin synthesis. 2022. 2022.","DOI":"10.1155\/2022\/4476339"},{"issue":"13","key":"3873_CR64","doi-asserted-by":"publisher","first-page":"3869","DOI":"10.1021\/jm9001764","volume":"52","author":"Y Song","year":"2009","unstructured":"Song Y, et al. Inhibition of staphyloxanthin virulence factor biosynthesis in Staphylococcus aureus: in vitro, in vivo, and crystallographic results. J Med Chem. 2009;52(13):3869\u201380.","journal-title":"J Med Chem"},{"issue":"3","key":"3873_CR65","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/antibiotics11030298","volume":"11","author":"RA Elmesseri","year":"2022","unstructured":"Elmesseri RA, et al. Staphyloxanthin as a potential novel target for deciphering promising anti-Staphylococcus aureus agents. Antibiotics (Basel). 2022;11(3):298.","journal-title":"Antibiotics (Basel)"},{"key":"3873_CR66","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1007\/s00284-012-0229-x","volume":"65","author":"JH Lee","year":"2012","unstructured":"Lee JH, et al. Flavone reduces the production of virulence factors, staphyloxanthin and \u03b1-hemolysin, in Staphylococcus aureus. Curr Microbiol. 2012;65:726\u201332.","journal-title":"Curr Microbiol"},{"key":"3873_CR67","doi-asserted-by":"crossref","unstructured":"Dinges MM, PM Orwin, P.M.J.C.m.r. Schlievert, Exotoxins of Staphylococcus aureus. 2000. 13(1): p. 16\u201334.","DOI":"10.1128\/CMR.13.1.16"},{"issue":"1","key":"3873_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/08927014.2014.991319","volume":"31","author":"HS Cho","year":"2015","unstructured":"Cho HS, et al. Red wines and flavonoids diminish Staphylococcus aureus virulence with anti-biofilm and anti-hemolytic activities. Biofouling. 2015;31(1):1\u201311.","journal-title":"Biofouling"},{"issue":"24","key":"3873_CR69","doi-asserted-by":"publisher","first-page":"7577","DOI":"10.3390\/molecules26247577","volume":"26","author":"S He","year":"2021","unstructured":"He S, et al. Suppressing alpha-hemolysin as potential target to screen of flavonoids to combat bacterial coinfection. Molecules. 2021;26(24):7577.","journal-title":"Molecules"},{"key":"3873_CR70","doi-asserted-by":"publisher","first-page":"7579808","DOI":"10.1155\/2018\/7579808","volume":"2018","author":"O Ping","year":"2018","unstructured":"Ping O, et al. Subinhibitory concentrations of prim-o-glucosylcimifugin decrease the expression of alpha-hemolysin in Staphylococcus aureus (USA300). Evid Based Complement Alternat Med. 2018;2018:7579808.","journal-title":"Evid Based Complement Alternat Med"},{"key":"3873_CR71","doi-asserted-by":"crossref","unstructured":"Saritha K, et al. Mechanism of antibacterial action of the alcoholic extracts of Hemidesmus indicus (L.) R. Br. ex Schult, Leucas aspera (Wild.), Plumbago zeylanica L., and Tridax procumbens (L.) R. Br. ex Schult. 2015. 6: p. 577.","DOI":"10.3389\/fmicb.2015.00577"},{"issue":"22","key":"3873_CR72","doi-asserted-by":"publisher","first-page":"123","DOI":"10.4103\/phrev.phrev_43_16","volume":"11","author":"OA Aldulaimi","year":"2017","unstructured":"Aldulaimi OA. General overview of phenolics from plant to laboratory, good antibacterials or not. Pharmacogn Rev. 2017;11(22):123.","journal-title":"Pharmacogn Rev"},{"issue":"1","key":"3873_CR73","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3390\/pathogens13010076","volume":"13","author":"A Kaushik","year":"2024","unstructured":"Kaushik A, et al. Biofilm Producing Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Humans: Clinical Implications and Management. Pathogens. 2024;13(1):76.","journal-title":"Pathogens"},{"key":"3873_CR74","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1590\/1519-6984.220259","volume":"81","author":"K Silva","year":"2020","unstructured":"Silva K, et al. Phytochemical characterization, antioxidant potential and antimicrobial activity of Averrhoa carambola L.(Oxalidaceae) against multiresistant pathogens. Braz J Biol. 2020;81:509\u201315.","journal-title":"Braz J Biol"},{"issue":"6","key":"3873_CR75","doi-asserted-by":"publisher","first-page":"4076","DOI":"10.1016\/S0006-3495(03)74820-6","volume":"85","author":"P Sch\u00e4r-Zammaretti","year":"2003","unstructured":"Sch\u00e4r-Zammaretti P, Ubbink J. The cell wall of lactic acid bacteria: surface constituents and macromolecular conformations. Biophys J. 2003;85(6):4076\u201392.","journal-title":"Biophys J"},{"key":"3873_CR76","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.foodcont.2018.09.021","volume":"96","author":"K Li","year":"2019","unstructured":"Li K, et al. Antibacterial activity and mechanism of a laccase-catalyzed chitosan\u2013gallic acid derivative against Escherichia coli and Staphylococcus aureus. Food Control. 2019;96:234\u201343.","journal-title":"Food Control"},{"issue":"1","key":"3873_CR77","first-page":"109","volume":"35","author":"WR Diao","year":"2014","unstructured":"Diao WR, et al. Chemical composition, antibacterial activity and mechanism of action of essential oil from seeds of fennel (Foeniculum vulgare Mill.). J Gastrointest Cancer. 2014;35(1):109\u201316.","journal-title":"J Gastrointest Cancer"},{"issue":"21","key":"3873_CR78","doi-asserted-by":"publisher","first-page":"7342","DOI":"10.3390\/molecules27217342","volume":"27","author":"M Xi","year":"2022","unstructured":"Xi M, et al. Potential application of luteolin as an active antibacterial composition in the development of hand sanitizer products. Molecules. 2022;27(21):7342.","journal-title":"Molecules"}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-025-03873-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12866-025-03873-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-025-03873-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T09:56:20Z","timestamp":1743501380000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmicrobiol.biomedcentral.com\/articles\/10.1186\/s12866-025-03873-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3873"],"URL":"https:\/\/doi.org\/10.1186\/s12866-025-03873-0","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,31]]},"assertion":[{"value":"4 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol of the study was approved by the Research Ethics Committee at the Faculty of Pharmacy, Cairo University, Egypt (Approval Numbers: MI 3053).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"182"}}