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Treatment is challenging due to multi-resistant strains and the ability of S. aureus to adhere and form biofilms on bone and implant surfaces. The present work involved the preparation and evaluation of a novel dual polymeric film coating on stainless steel. Chitosan and polycaprolactone (PCL) multilayers, loaded with poly\u00ad(methyl methacrylate) (PMMA) microspheres encapsulating vancomycin or daptomycin, produced by the dip-coating technique, allowed local antibiotic-controlled delivery for the treatment of implant-related infections. Enhanced adhesion of the film to the metal substrate surface was achieved by mechanical abrasion of its surface. Studies have shown that for both drugs the release occurs by diffusion, but the release profile depends on the type of drug (daptomycin or vancomycin), the pH of the solution, and whether the drug is freestanding (directly incorporated into the films) or encapsulated in PMMA microspheres. Daptomycin freestanding films reached 90% release after 1 day at pH 7.4 and 4 days at pH 5.5. In comparison, films with daptomycin encapsulated microspheres reached 90% release after 2 h at pH 5.5 and 2 days at pH 7.4. Vancomycin encapsulated and freestanding films showed a similar behavior reaching 90% release after 20 h of release at pH 5.5 and 2 and 3 days, respectively, at pH 7.4. Furthermore, daptomycin-loaded films showed activity (assessed by agar diffusion assays) against sensitive (ATCC 25923) and clinically isolated (MRSA) S. aureus strains.<\/jats:p>","DOI":"10.1021\/acsomega.2c00504","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T19:50:13Z","timestamp":1656445813000},"page":"23096-23106","source":"Crossref","is-referenced-by-count":34,"title":["Drug Delivery from PCL\/Chitosan Multilayer Coatings\nfor Metallic Implants"],"prefix":"10.1021","volume":"7","author":[{"given":"I\u0301ris","family":"Soares","sequence":"first","affiliation":[{"name":"Universidade Nova de Lisboa , , Campus de Caparica , ,","place":["Caparica, Portugal, 2829-516"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Faria","sequence":"additional","affiliation":[{"name":"Universidade Nova de Lisboa , , Campus de Caparica , ,","place":["Caparica, Portugal, 2829-516"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Marques","sequence":"additional","affiliation":[{"name":"Universidade Nova de Lisboa , , Campus de Caparica , ,","place":["Caparica, Portugal, 2829-516"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7110-6393","authenticated-orcid":true,"given":"Isabel A. C.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Universidade de Lisboa , , Avenida Prof. Gama Pinto , ,","place":["Lisboa, Portugal, 1649-003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7810-1747","authenticated-orcid":true,"given":"Carlos","family":"Baleiza\u0303o","sequence":"additional","affiliation":[{"name":"Universidade de Lisboa , , ,","place":["Lisboa, Portugal, 1049-001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-5892","authenticated-orcid":true,"given":"Ana","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Universidade de Lisboa , , Avenida Prof. Gama Pinto , ,","place":["Lisboa, Portugal, 1649-003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8838-0364","authenticated-orcid":true,"given":"Isabel M. M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universidade Nova de Lisboa , , Campus de Caparica , ,","place":["Caparica, Portugal, 2829-516"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1631-6248","authenticated-orcid":true,"given":"Ana Catarina","family":"Baptista","sequence":"additional","affiliation":[{"name":"Universidade Nova de Lisboa , , Campus de Caparica , ,","place":["Caparica, Portugal, 2829-516"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"2026081710140325300_cit1","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/S0140-6736(04)16727-5","article-title":"Osteomyelitis","volume":"364","author":"Lew","year":"2004","journal-title":"Lancet"},{"key":"2026081710140325300_cit2","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41579-018-0019-y","article-title":"Implant Infections: Adhesion, Biofilm\nFormation and Immune Evasion","volume":"16","author":"Arciola","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"2026081710140325300_cit3","doi-asserted-by":"publisher","first-page":"3174","DOI":"10.1016\/j.biomaterials.2013.01.074","article-title":"The Future of Biologic Coatings for\nOrthopaedic Implants Stuart","volume":"34","author":"Goodman","year":"2013","journal-title":"Biomaterials"},{"key":"2026081710140325300_cit4","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1097\/INF.0000000000001812","article-title":"Postoperative Spinal\nImplant Infections in Children","volume":"37","author":"Lamberet","year":"2018","journal-title":"Pediatr. Infect.\nDis. J."},{"key":"2026081710140325300_cit5","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1111\/prd.12149","article-title":"Treatment of Pathologic\nPeri-Implant Pockets","volume":"76","author":"Renvert","year":"2018","journal-title":"Peridontol. 2000"},{"key":"2026081710140325300_cit6","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01379-18","article-title":"Improving\nthe Diagnosis of Orthopedic Implant-Associated Infections: Optimizing\nthe Use of Tools Already in the Box","volume":"56","author":"Vasoo","year":"2018","journal-title":"J. Clin.\nMicrobiol."},{"key":"2026081710140325300_cit7","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.1016\/j.msec.2009.07.014","article-title":"Local Antibiotic Delivery\nSystems for the Treatment of Osteomyelitis\n- A Review","volume":"29","author":"Nandi","year":"2009","journal-title":"Mater. Sci. Eng. 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Res."},{"key":"2026081710140325300_cit10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/B978-0-12-385099-7.00004-8","article-title":"Biomass-Derived Syngas Fermentation\ninto Biofuels","volume":"101","author":"Munasinghe","year":"2011","journal-title":"Biofuels"},{"key":"2026081710140325300_cit11","doi-asserted-by":"publisher","first-page":"17089","DOI":"10.1021\/acsami.8b04045","article-title":"Metal TiO 2 Nanotube Layers for the Treatment\nof Dental Implant Infections","volume":"10","author":"Roguska","year":"2018","journal-title":"Appl. Mater. Interfaces"},{"key":"2026081710140325300_cit12","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.porgcoat.2018.04.028","article-title":"Dual Nanofibrous\nBioactive Coating and Antimicrobial Surface Treatment for Infection\nResistant Titanium Implants","volume":"121","author":"Kiran","year":"2018","journal-title":"Prog. Org. 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Surg."},{"key":"2026081710140325300_cit19","doi-asserted-by":"publisher","first-page":"5969","DOI":"10.1016\/j.biomaterials.2013.04.036","article-title":"Multilayered Coating on Titanium\nfor Controlled Release of Antimicrobial Peptides for the Prevention\nof Implant-Associated Infections","volume":"34","author":"Kazemzadeh-Narbat","year":"2013","journal-title":"Biomaterials"},{"key":"2026081710140325300_cit20","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.biomaterials.2004.03.031","article-title":"Nitric\nOxide-Releasing Sol-Gels as\nAntibacterial Coatings for Orthopedic Implants","volume":"26","author":"Nablo","year":"2005","journal-title":"Biomaterials"},{"key":"2026081710140325300_cit21","doi-asserted-by":"publisher","first-page":"37511","DOI":"10.1021\/acsami.7b13565","article-title":"Smart Antibacterial\nSurfaces with Switchable Bacteria-Killing and Bacteria-Releasing Capabilities","volume":"9","author":"Wei","year":"2017","journal-title":"Appl. Mater. Interfaces"},{"key":"2026081710140325300_cit22","doi-asserted-by":"publisher","DOI":"10.3390\/coatings11060649","article-title":"Innovative Coatings\nof Metallic Alloys Used as Bioactive Surfaces in Implantology: A Review","volume":"11","author":"Prodana","year":"2021","journal-title":"Coatings"},{"key":"2026081710140325300_cit23","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.actbio.2011.10.016","article-title":"Calcium Phosphate\nCoatings on Magnesium Alloys for\nBiomedical Applications: A Review","volume":"8","author":"Shadanbaz","year":"2012","journal-title":"Acta Biomater."},{"key":"2026081710140325300_cit24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2021.129071","article-title":"Antimicrobial\nTiO2 Nanocomposite Coatings for Surfaces, Dental and Orthopaedic Implants","volume":"416","author":"Kumaravel","year":"2021","journal-title":"Chem. Eng. J."},{"key":"2026081710140325300_cit25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82992-w","article-title":"An Antibacterial\nCoated Polymer Prevents Biofilm Formation and Implant-Associated Infection","volume":"11","author":"Ishihama","year":"2021","journal-title":"Sci. Rep."},{"key":"2026081710140325300_cit26","article-title":"Orthopedic Implant\nMaterials","volume-title":"StatPearls [Internet]","author":"Tapscott","year":"2022"},{"key":"2026081710140325300_cit27","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.ijpharm.2015.03.016","article-title":"Improvement\nof the Antibacterial\nActivity of Daptomycin-Loaded Polymeric Microparticles by Eudragit\nRL 100: An Assessment by Isothermal Microcalorimetry","volume":"485","author":"Ferreira","year":"2015","journal-title":"Int. J. Pharm."},{"key":"2026081710140325300_cit28","doi-asserted-by":"publisher","first-page":"4351","DOI":"10.2147\/IJN.S84108","article-title":"Activity\nof daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles\nagainst mature staphylococcal biofilms","author":"Bettencourt","year":"2015","journal-title":"Int.\nJ. Nanomed."},{"key":"2026081710140325300_cit29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55355-9","article-title":"Quantitative Peel Test for Thin Films\/Layers Based\non a Coupled Parametric and Statistical Study","volume":"9","author":"Rezaee","year":"2019","journal-title":"Sci. Rep."},{"key":"2026081710140325300_cit30","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.1016\/j.biomaterials.2006.01.017","article-title":"How Useful Is SBF in\nPredicting in Vivo Bone Bioactivity?","volume":"27","author":"Kokubo","year":"2006","journal-title":"Biomaterials"},{"key":"2026081710140325300_cit31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.msec.2019.03.056","article-title":"Engineering\na Multifunctional 3D-Printed PLA-Collagen-Minocycline-NanoHydroxyapatite\nScaffold with Combined Antimicrobial and Osteogenic Effects for Bone\nRegeneration","volume":"101","author":"Martin","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"2026081710140325300_cit32","doi-asserted-by":"publisher","first-page":"055303","DOI":"10.1088\/1464-4258\/10\/5\/055303","article-title":"Raman spectra of polymethyl methacrylate\noptical fibres excited by a 532 nm diode pumped solid state laser","volume":"10","author":"Thomas","year":"2008","journal-title":"J. Opt. A Pure Appl. Opt."},{"key":"2026081710140325300_cit33","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1002\/jrs.4335","article-title":"Raman Spectroscopy of Proteins: A\nReview","volume":"44","author":"Rygula","year":"2013","journal-title":"J. Raman Spectrosc."},{"key":"2026081710140325300_cit34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/B978-0-08-100092-2.00005-9","article-title":"Mathematical Models of Drug Release","volume-title":"Strategies\nto Modify the Drug Release from Pharmaceutical Systems","year":"2015"},{"key":"2026081710140325300_cit35","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1111\/cbdd.13427","article-title":"A Rapid Method for Estimation of\nthe Efficacy of Potential Antimicrobials in Humans and Animals by\nAgar Diffusion Assay","volume":"93","author":"Salina","year":"2019","journal-title":"Chem. Biol. Drug Des."},{"key":"2026081710140325300_cit36","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.6749","article-title":"Minimum Inhibitory Concentrations\nof Vancomycin and Daptomycin Against Methicillin-Resistant Staphylococcus Aureus Isolated from Various Clinical\nSpecimens: A Study from South India","volume":"12","author":"Moses","year":"2020","journal-title":"Cureus"},{"key":"2026081710140325300_cit37","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1128\/AAC.01491-05","article-title":"Daptomycin Bactericidal\nActivity\nand Correlation between Disk and Broth Microdilution Method Results\nin Testing of Staphylococcus Aureus Strains with Decreased Susceptibility to Vancomycin","volume":"50","author":"Sader","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081710140325300_cit38","volume-title":"CLSI M100-ED29: 2019\nPerformance Standards for Antimicrobial Susceptibility Testing, 29th\nEdition","author":"Weinstein","year":"2020","edition":"30"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.2c00504","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/7\/27\/23096\/3643523\/ao2c00504.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/7\/27\/23096\/3643523\/ao2c00504.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:29:54Z","timestamp":1786976994000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/7\/27\/23096\/379269\/Drug-Delivery-from-PCL-Chitosan-Multilayer"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,28]]},"references-count":38,"journal-issue":{"issue":"27","published-online":{"date-parts":[[2022,6,28]]},"published-print":{"date-parts":[[2022,7,12]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.2c00504","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,28]]}}}