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Surfactants play a key role as coating agents for several nanoparticle types, modulating interfacial interactions with drugs and the environment. Specifically, levofloxacin (LV) inhalation can benefit from its loading into nanostructured lipid carriers (NLCs) for high drug entrapment, sustained release, and antimicrobial efficacy, but no studies have focused on the relevance of the surfactant type on its biological and physicochemical performance. Therefore, this study aimed to evaluate the impact of three nonionic surfactants\u2500polysorbate 80 (P80), poloxamer 407 (P407), and poloxamer 188 (P188)\u2500on the physicochemical and biological in vitro performance of LV-loaded NLCs. NLCs presented similar physicochemical properties, with average sizes of 100\u2013200 nm, polydispersity &amp;lt;0.3, slightly negative \u03b6-potential (\u22125 to \u221219 mV), high drug entrapment efficiency (&amp;gt;77%), and rounded-shape morphology. The P188 coating tends to have a prolonged release profile compared to the other formulations, but further studies should be conducted to confirm this tendency. All formulations preserved the antimicrobial activity of LV in vitro compared to the free LV against Klebsiella pneumoniae, Staphylococcus aureus, Burkholderia cepacia, and Haemophilus influenzae. Notably, P407 was the only surfactant able to maintain the biofilm inhibition of B. cepacia promoted by LV up to half the minimum inhibitory concentration (MIC) under the tested conditions. This is the first evidence of LV efficacy against biofilms of this species, highlighting the importance of LV application against this undervalued but deadly infection agent in patients with cystic fibrosis. Concerning device compatibility, P407-stabilized NLCs retained their size and PDI within the same range after nebulization through a vibrating mesh, which is favorable for future pulmonary delivery. In summary, these findings highlight the importance of surfactant type selection, indicating the preliminary feasibility of the P407-based formulation and providing a foundation for future investigations on the pulmonary delivery of LV.<\/jats:p>","DOI":"10.1021\/acsomega.6c01967","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T21:02:19Z","timestamp":1786654939000},"page":"49255-49267","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Surfactants\nin Tailoring Nanostructured\nLipid Carriers for Inhaled Levofloxacin"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-5208","authenticated-orcid":true,"given":"Viviane Lucia","family":"Beraldo de Araujo","sequence":"first","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-852"]},{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3081-2056","authenticated-orcid":true,"given":"Samira Elisa","family":"Alves Geraldo","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]},{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-888"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"van Vliet Lima","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]},{"name":"Sanofi Medley Farmace\u0302utica Ltda , ,","place":["Campinas, Brazil, 13080-010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel da Silva","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-5851","authenticated-orcid":true,"given":"Joa\u0303o Paulo","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Lancellotti","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-8702","authenticated-orcid":true,"given":"Karina","family":"Cogo-Mu\u0308ller","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Raposo","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Oliveira-Nascimento","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas , , ,","place":["Campinas, Brazil, 13083-871"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"issue":"6","key":"2026083119121947400_cit1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1053\/j.semdp.2017.06.001","article-title":"The Pathology of Pulmonary Bacterial Infection","volume":"34","author":"Kradin","year":"2017","journal-title":"Semin. Diagn. Pathol."},{"issue":"5","key":"2026083119121947400_cit2","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1021\/acs.molpharmaceut.8b01256","article-title":"Tailored\nNanocarriers for the Pulmonary Delivery of Levofloxacin against Pseudomonas\nAeruginosa: A Comparative Study","volume":"16","author":"Derbali","year":"2019","journal-title":"Mol. Pharmaceutics"},{"key":"2026083119121947400_cit3","unstructured":"Burkholderia\ncepacia complex infections: More complex than the bacterium\nname suggest - Journal of Infection; https:\/\/www.journalofinfection.com\/article\/S0163-4453(18)30218-4\/abstract, (accessed 2026\u201305\u201311)."},{"key":"2026083119121947400_cit4","doi-asserted-by":"publisher","first-page":"S115","DOI":"10.1016\/j.ijantimicag.2006.06.001","article-title":"Respiratory\nTract Infections: At-Risk Patients, Who Are They?Implications for\nTheir Management with Levofloxacin","volume":"28","author":"Canton","year":"2006","journal-title":"Int. J.\nAntimicrob. 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Care Med."},{"issue":"8","key":"2026083119121947400_cit6","doi-asserted-by":"publisher","first-page":"826","DOI":"10.3390\/antibiotics14080826","article-title":"Diminishing\nEfficacy of Second-Line\nLevofloxacin-Based Quadruple Therapy in Helicobacter Pylori Eradication:\nA Prospective Real-World Study in Vietnam Amid Rising Antibiotic Resistance","volume":"14","author":"Vo","year":"2025","journal-title":"Antibiotics"},{"issue":"9","key":"2026083119121947400_cit7","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.jsps.2021.07.015","article-title":"Nanostructured Lipid Carriers (NLCs)\nas Drug Delivery\nPlatform: Advances in Formulation and Delivery Strategies","volume":"29","author":"Elmowafy","year":"2021","journal-title":"Saudi Pharm. 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J. Pharm."},{"issue":"10","key":"2026083119121947400_cit16","doi-asserted-by":"publisher","first-page":"3833","DOI":"10.1002\/jps.23251","article-title":"Nanostructured Lipid Carriers as\nNovel Ophthalmic Delivery System for Mangiferin: Improving in Vivo\nOcular Bioavailability","volume":"101","author":"Liu","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"2026083119121947400_cit17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1533\/9781908818683.219","article-title":"Lipids and\nInorganic Nanoparticles in Oral Insulin Delivery","volume-title":"Oral Delivery of Insulin","author":"Sonia","year":"2014"},{"key":"2026083119121947400_cit18","doi-asserted-by":"publisher","first-page":"3937","DOI":"10.2147\/IJN.S298606","article-title":"A Critical\nReview of the Use of Surfactant-Coated Nanoparticles in Nanomedicine\nand Food Nanotechnology","volume":"16","author":"Miyazawa","year":"2021","journal-title":"Int. J. Nanomed."},{"issue":"3","key":"2026083119121947400_cit19","doi-asserted-by":"publisher","first-page":"538","DOI":"10.3390\/pharmaceutics14030538","article-title":"To Enhance Mucus Penetration\nand Lung Absorption of Drug by Inhalable\nNanocrystals-In-Microparticles","volume":"14","author":"Huang","year":"2022","journal-title":"Pharmaceutics"},{"issue":"4","key":"2026083119121947400_cit20","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1601556","article-title":"Nanoparticles That\nDo Not Adhere to Mucus Provide Uniform and Long-Lasting Drug Delivery\nto Airways Following Inhalation","volume":"3","author":"Schneider","year":"2017","journal-title":"Sci. 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Pharm."},{"issue":"7","key":"2026083119121947400_cit24","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1038\/nprot.2008.75","article-title":"Neutral\nRed Uptake Assay for the\nEstimation of Cell Viability\/Cytotoxicity","volume":"3","author":"Repetto","year":"2008","journal-title":"Nat.\nProtoc."},{"key":"2026083119121947400_cit25","doi-asserted-by":"publisher","first-page":"106576","DOI":"10.1016\/j.vascn.2019.04.002","article-title":"In Vitro Model for Predicting Acute\nInhalation Toxicity by Using a Calu-3 Epithelium Cytotoxicity Assay","volume":"98","author":"Jeong","year":"2019","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"2026083119121947400_cit26","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1208\/s12248-011-9317-2","article-title":"Modification\nof Disodium Cromoglycate Passage Across Lung Epithelium In Vitro Via\nIncorporation into Polymeric Microparticles","volume":"14","author":"Haghi","year":"2012","journal-title":"Aaps J."},{"key":"2026083119121947400_cit27","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ejpb.2021.07.016","article-title":"A Comparison of Three Mucus-Secreting\nAirway Cell Lines (Calu-3, SPOC1 and UNCN3T) for Use as Biopharmaceutical\nModels of the Nose and Lung","volume":"167","author":"Lee","year":"2021","journal-title":"Eur. J. Pharm.\nBiopharm."},{"issue":"1\u20132","key":"2026083119121947400_cit28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0378-5173(00)00452-X","article-title":"Characterization\nof the Calu-3 Cell Line as a Tool to Screen Pulmonary Drug Delivery","volume":"208","author":"Foster","year":"2000","journal-title":"Int. J. Pharm."},{"key":"2026083119121947400_cit29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejps.2014.12.017","article-title":"The Characterization\nof the Human Cell Line Calu-3 under Different Culture Conditions and\nIts Use as an Optimized in Vitro Model to Investigate Bronchial Epithelial\nFunction","volume":"69","author":"Kreft","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"issue":"1\u20133","key":"2026083119121947400_cit30","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.colsurfa.2007.08.005","article-title":"Effect of Surfactants\non the Formation and Characterization of a New Type of Colloidal Drug\nDelivery System: Nanostructured Lipid Carriers","volume":"315","author":"Han","year":"2008","journal-title":"Colloids Surf., A"},{"issue":"5","key":"2026083119121947400_cit31","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1016\/j.xphs.2018.01.005","article-title":"Surfactant Effects on Lipid-Based\nVesicles Properties","volume":"107","author":"Bnyan","year":"2018","journal-title":"J. Pharm. Sci."},{"issue":"8","key":"2026083119121947400_cit32","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1016\/j.apsb.2019.10.002","article-title":"Comparative Study of\nMucoadhesive and Mucus-Penetrative Nanoparticles Based on Phospholipid\nComplex to Overcome the Mucus Barrier for Inhaled Delivery of Baicalein","volume":"10","author":"Dong","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"2026083119121947400_cit33","unstructured":"Lipid Nanoparticles: Production, Characterization\nand Stability; Springer Nature Link, https:\/\/link.springer.com\/book\/10.1007\/978-3-319-10711-0, (accessed\n2026\u201305\u201311)."},{"key":"2026083119121947400_cit34","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jddst.2019.02.017","article-title":"Nanostructured Lipid\nCarriers (NLC) System: A Novel Drug Targeting\nCarrier","volume":"51","author":"Salvi","year":"2019","journal-title":"J. Drug Delivery Sci. Technol."},{"issue":"2","key":"2026083119121947400_cit35","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.xphs.2021.08.017","article-title":"Characterization of\nPolysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand\nIts Susceptibility to Degradation and Its Oxidative Degradation Pathway","volume":"111","author":"Liu","year":"2022","journal-title":"J. Pharm. Sci."},{"issue":"1","key":"2026083119121947400_cit36","doi-asserted-by":"publisher","first-page":"3621","DOI":"10.1038\/s41598-019-40201-9","article-title":"The Degradation\nof Levofloxacin in\nInfusions Exposed to Daylight with an Identification of a Degradation\nProduct with HPLC-MS","volume":"9","author":"Czyrski","year":"2019","journal-title":"Sci. Rep."},{"issue":"6","key":"2026083119121947400_cit37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156690","article-title":"Comparative Activity\nof Ciprofloxacin, Levofloxacin and Moxifloxacin against Klebsiella\nPneumoniae, Pseudomonas Aeruginosa and Stenotrophomonas Maltophilia\nAssessed by Minimum Inhibitory Concentrations and Time-Kill Studies","volume":"11","author":"Grillon","year":"2016","journal-title":"PLoS One"},{"issue":"2","key":"2026083119121947400_cit38","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.diagmicrobio.2016.11.008","article-title":"Polysorbate\n80 and Polymyxin B Inhibit\nStenotrophomonas Maltophilia Biofilm","volume":"87","author":"Malinowski","year":"2017","journal-title":"Diagn.\nMicrobiol. Infect. 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J."},{"issue":"4","key":"2026083119121947400_cit41","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1080\/17425247.2016.1213239","article-title":"Sustained-Release Drug\nDelivery of Antimicrobials in\nControlling of Supragingival Oral Biofilms","volume":"14","author":"Steinberg","year":"2017","journal-title":"Expert Opin. Drug Delivery"},{"key":"2026083119121947400_cit42","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jddst.2018.06.012","article-title":"Cancer\nChemotherapy: Effect of Poloxamer Modified Nanoparticles\non Cellular Function","volume":"47","author":"Allotey-Babington","year":"2018","journal-title":"J. Drug Delivery Sci.\nTechnol."},{"issue":"4","key":"2026083119121947400_cit43","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.cell.2018.03.028","article-title":"Chemistry-First Approach\nfor Nomination of Personalized Treatment in Lung Cancer","volume":"173","author":"McMillan","year":"2018","journal-title":"Cell"},{"issue":"2","key":"2026083119121947400_cit44","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3390\/jfb5020043","article-title":"HaCaT Keratinocytes\nResponse on Antimicrobial Atelocollagen Substrates: Extent of Cytotoxicity,\nCell Viability and Proliferation","volume":"5","author":"Lo\u0301pez-Garci\u0301a","year":"2014","journal-title":"J. Funct.\nBiomater."},{"issue":"2","key":"2026083119121947400_cit45","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1089\/089426802320282257","article-title":"Drug Absorption\nby the Respiratory Mucosa: Cell Culture Models and Particulate Drug\nCarriers","volume":"15","author":"Ehrhardt","year":"2002","journal-title":"J. Aerosol Med."},{"key":"2026083119121947400_cit46","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ejps.2018.01.018","article-title":"In Vitro Lung Epithelial\nCell Transport and Anti-Interleukin-8\nReleasing Activity of Liposomal Ciprofloxacin","volume":"115","author":"Darweesh","year":"2018","journal-title":"Eur. J. Pharm. 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