{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:50:31Z","timestamp":1777499431615,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-QUI\/31721\/2017"],"award-info":[{"award-number":["PTDC\/MED-QUI\/31721\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PPBI-POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["PPBI-POCI-01-0145-FEDER-022122"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SAICTPAC\/0019\/2015"],"award-info":[{"award-number":["SAICTPAC\/0019\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04138\/2020"],"award-info":[{"award-number":["UIDB\/04138\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIBD\/00276\/2020"],"award-info":[{"award-number":["UIBD\/00276\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04138\/2020"],"award-info":[{"award-number":["UIDP\/04138\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["DL57\/2016\/CP1438\/CT0002"],"award-info":[{"award-number":["DL57\/2016\/CP1438\/CT0002"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005765","name":"Universidade de Lisboa","doi-asserted-by":"publisher","award":["PhD fellowship BD\/2018"],"award-info":[{"award-number":["PhD fellowship BD\/2018"]}],"id":[{"id":"10.13039\/501100005765","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 \u00b5g\/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed.<\/jats:p>","DOI":"10.3390\/pharmaceutics13030321","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T05:17:16Z","timestamp":1614662236000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms"],"prefix":"10.3390","volume":"13","author":[{"given":"Magda","family":"Ferreira","sequence":"first","affiliation":[{"name":"Centre for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-9459","authenticated-orcid":false,"given":"Sandra N.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3821-419X","authenticated-orcid":false,"given":"Frederico","family":"Aires-da-Silva","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-5892","authenticated-orcid":false,"given":"Ana","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"given":"Sandra I.","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6814-7226","authenticated-orcid":false,"given":"Maria Manuela","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/apm.12687","article-title":"Orthopaedic biofilm infections","volume":"125","author":"Zimmerli","year":"2017","journal-title":"APMIS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100739","DOI":"10.1016\/j.genrep.2020.100739","article-title":"Staphylococcus aureus biofilms: Structures, antibiotic resistance, inhibition, and vaccines","volume":"20","author":"Parastan","year":"2020","journal-title":"Gene Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1042\/EBC20160061","article-title":"Antibiotic tolerance and the alternative lifestyles of Staphylococcus aureus","volume":"61","author":"Bui","year":"2017","journal-title":"Essays Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1002\/bies.201400080","article-title":"Staphylococcus aureus chronic and relapsing infections: Evidence of a role for persister cells","volume":"36","author":"Conlon","year":"2014","journal-title":"BioEssays"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.3389\/fmicb.2017.02409","article-title":"Combination Strategies to Enhance the Efficacy of Antimicrobial Peptides against Bacterial Biofilms","volume":"8","author":"Grassi","year":"2017","journal-title":"Front. 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