{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:15:49Z","timestamp":1791476149802,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","award":["6035"],"award-info":[{"award-number":["6035"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Metallic nanoparticles, such as gold nanoparticles (AuNPs), have been extensively studied as drug delivery systems for various therapeutic applications. However, drug-loaded-AuNPs have been rarely explored in vivo for their effect on bacteria residing inside tissues. Ciprofloxacin (CIP) is a second-generation fluoroquinolone with a broad-spectrum of antibiotic properties devoid of developing bacteria resistance. This research is focused on the synthesis and physical characterization of Ciprofloxacin-loaded gold nanoparticles (CIP-AuNPs) and their effect on the colonization of Enterococcus faecalis in the liver and kidneys of mice. The successfully prepared CIP-AuNPs were stable and exerted enhanced in vitro antibacterial activity against E. faecalis compared with free CIP. The optimized CIP-AuNPs were administered (500 \u00b5g\/Kg) once a day via tail vein to infected mice for eight days and were found to be effective in eradicating E. faecalis from the host tissues. Moreover, unlike CIP, CIP-AuNPs were non-hemolytic. In summary, this study demonstrated that CIP-AuNPs are promising and biocompatible alternative therapeutics for E.-faecalis-induced infections resistant to conventional drugs (e.g., beta-lactams and vancomycin) and should be further investigated.<\/jats:p>","DOI":"10.3390\/nano11113152","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:56Z","timestamp":1638314576000},"page":"3152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Ciprofloxacin-Loaded Gold Nanoparticles against Antimicrobial Resistance: An In Vivo Assessment"],"prefix":"10.3390","volume":"11","author":[{"given":"Afrah","family":"Nawaz","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Mohsin","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nosheen Fatima","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6807-0054","authenticated-orcid":false,"given":"Tahreem","family":"Tanweer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Batool","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-5969","authenticated-orcid":false,"given":"Thomas J.","family":"Webster","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-7322","authenticated-orcid":false,"given":"Farid","family":"Menaa","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine and Nanomedicine, California Innovations Corporation, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundus","family":"Riaz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhat","family":"Batool","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuba","family":"Maryam","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqra","family":"Shafique","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abida","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1476-615X","authenticated-orcid":false,"given":"Arfa","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Sciences, School of Mechanical & Manufacturing Engineering, National University of Science & Technology, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.joen.2013.08.022","article-title":"Evaluation of the Antibacterial Efficacy of Silver Nanoparticles against Enterococcus faecalis Biofilm","volume":"40","author":"Wu","year":"2014","journal-title":"J. Endod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.joen.2005.10.022","article-title":"Prevalence of Enterococcus faecalis at Multiple Oral Sites in Endodontic Patients Using Culture and PCR","volume":"32","author":"Sedgley","year":"2006","journal-title":"J. Endod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.0143-2885.2004.00785.x","article-title":"Survival of Enterococcus faecalis in infected dentinal tu-bules after root canal filling with different root canal sealers in vitro","volume":"37","author":"Saleh","year":"2004","journal-title":"Int. Endod. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.joen.2009.11.016","article-title":"Biofilm Formation Capability of Enterococcus faecalis Cells in Starvation Phase and Its Susceptibility to Sodium Hypochlorite","volume":"36","author":"Liu","year":"2010","journal-title":"J. Endod."},{"key":"ref_5","unstructured":"Gilmore, M.S., Clewell, D.B., Ike, Y., and Shankar, N. (2014). Enterococci: From Commensals to Leading Causes of Drug Resistant Infection, Eye and Ear Infirmary."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1093\/jac\/dkr262","article-title":"Discovery research: The scientific challenge of finding new antibiotics","volume":"66","author":"Livermore","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1093\/femsre\/fuz021","article-title":"Impact of nanosystems in Staphylococcus aureus biofilms treatment","volume":"43","author":"Pinto","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Vassallo, A., Silletti, M.F., Faraone, I., and Milella, L. (2020). Nanoparticulate Antibiotic Systems as Antibacterial Agents and Antibiotic Delivery Platforms to Fight Infections. J. Nanomater., 2020.","DOI":"10.1155\/2020\/6905631"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.micpath.2018.06.016","article-title":"Photocatalytic properties and antimicrobial ef-ficacy of Fe doped CuO nanoparticles against the pathogenic bacteria and fungi","volume":"122","author":"Pugazhendhi","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Uzair, B., Liaqat, A., Iqbal, H., Menaa, B., Razzaq, A., Thiripuranathar, G., Rana, N.F., and Menaa, F. (2020). Green and Cost-Effective Synthesis of Metallic Nanoparticles by Algae: Safe Methods for Translational Medicine. Bioengineering, 7.","DOI":"10.3390\/bioengineering7040129"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.2147\/IJN.S121956","article-title":"The antimicrobial activity of nanoparticles: Present situation and prospects for the future","volume":"12","author":"Wang","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1039\/C1CS15166E","article-title":"Gold nanoparticles in biomedical applications: Recent advances and perspectives","volume":"41","author":"Dykman","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S3029","DOI":"10.1016\/j.arabjc.2013.11.044","article-title":"Green biosynthesis of gold nanoparticles using Galaxaura elongata and characterization of their antibacterial activity","volume":"10","author":"Ibraheem","year":"2017","journal-title":"Arab. J. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8047","DOI":"10.2147\/IJN.S212750","article-title":"Near-infrared light-enhanced protease-conjugated gold nanorods as a photo-thermal antimicrobial agent for elimination of exotoxin and biofilms","volume":"14","author":"Li","year":"2019","journal-title":"International journal of nanomedicine. Int. J. Nanomed."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rhazouani, A., Gamrani, H., El Achaby, M., Aziz, K., Gebrati, L., Uddin, S., and Aziz, F. (2021). Synthesis and Toxicity of Graphene Oxide Nanoparticles: A Literature Review of In vitro and In vivo Studies. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/5518999"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40824-015-0032-4","article-title":"Evaluation of ciprofloxacin and metronidazole encapsulated biomimetic nanomatrix gel on Enterococcus faecalis and Treponema denticola","volume":"19","author":"Kaushik","year":"2015","journal-title":"Biomater. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Azad, A., Rostamifar, S., Modaresi, F., Bazrafkan, A., and Rezaie, Z. (2020). Assessment of the Antibacterial Effects of Bismuth Nanoparticles against Enterococcus faecalis. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/5465439"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Parolia, A., Kumar, H., Ramamurthy, S., Davamani, F., and Pau, A. (2020). Effectiveness of chitosan-propolis nanoparticle against Enterococcus faecalis biofilms in the root canal. BMC Oral Heal., 20.","DOI":"10.1186\/s12903-020-01330-0"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/iej.13436","article-title":"Doxycycline-functionalized polymeric nanoparticles inhibit Enterococcus faecalis biofilm formation on dentine","volume":"54","author":"Baca","year":"2021","journal-title":"Int. Endod. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.pdpdt.2019.05.042","article-title":"Synergistic effect of methylene blue and biogenic gold nanoparticles against Enterococcus faecalis","volume":"27","author":"Maliszewska","year":"2019","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.joen.2020.07.001","article-title":"Combined Effect of a Mixture of Silver Nanoparticles and Calcium Hydroxide against Enterococcus faecalis Biofilm","volume":"46","author":"Balto","year":"2020","journal-title":"J. Endod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.4103\/ccd.ccd_828_17","article-title":"Antibacterial efficacy of biosynthesized silver nanoparticles against Enterococcus faecalis Biofilm: An in vitro study","volume":"9","author":"Halkai","year":"2018","journal-title":"Contemp. Clin. Dent."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jds.2019.09.006","article-title":"Nano-graphene oxide with antisense walR RNA inhibits the pathogenicity of Enterococcus faecalis in periapical periodontitis","volume":"15","author":"Wu","year":"2019","journal-title":"J. Dent. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Martini, C., Longo, F., Castagnola, R., Marigo, L., Grande, N.M., Cordaro, M., Cacaci, M., Papi, M., Palmieri, V., and Bugli, F. (2020). Antimicrobial and Antibiofilm Properties of Graphene Oxide on Enterococcus faecalis. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100692"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3109\/21691401.2014.971807","article-title":"Current methods for synthesis of gold nanoparticles","volume":"44","author":"Herizchi","year":"2016","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1021\/la0358567","article-title":"Ciprofloxacin-protected gold nanopar-ticles","volume":"20","author":"Tom","year":"2004","journal-title":"Langmuir"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/02652048.2018.1523970","article-title":"Design of ciprofloxacin-loaded nano-and micro-composite particles for dry powder inhaler formulations: Preparation, in vitro characterisation, and antimicro-bial efficacy","volume":"35","author":"Topal","year":"2018","journal-title":"J. Microencapsul."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/10717544.2019.1701140","article-title":"Preparation of PLGA-chitosan based nanocarriers for enhancing anti-bacterial effect of ciprofloxacin in root canal infection","volume":"27","author":"Arafa","year":"2020","journal-title":"Drug Deliv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.joen.2014.12.025","article-title":"Effects of ciprof-loxacin-containing scaffolds on Enterococcus faecalis biofilms","volume":"41","author":"Albuquerque","year":"2015","journal-title":"J. Endod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.2147\/IJN.S140625","article-title":"Single-walled carbon nanotubes-ciprofloxacin nanoantibiotic: Strategy to improve ciprofloxacin antibacterial activity","volume":"12","author":"Assali","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1128\/IAI.01299-12","article-title":"Redox Balance via Lactate Dehydrogenase Is Important for Multiple Stress Resistance and Virulence in Enterococcus faecalis","volume":"81","author":"Rana","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_32","first-page":"217","article-title":"Kinetic modeling on drug release from controlled drug delivery systems","volume":"67","author":"Dash","year":"2010","journal-title":"Acta Pol. Pharm. Drug Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0168-3659(00)00366-7","article-title":"Translocation of drug particles in HPMC matrix gel layer: Effect of drug solubility and influence on release rate","volume":"70","author":"Bettini","year":"2001","journal-title":"J. Control. Release"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1477-3155-11-13","article-title":"Enhanced biocidal activity of Au nanoparticles synthesized in one pot using 2, 4-dihydroxybenzene carbodithioic acid as a reducing and stabilizing agent","volume":"11","author":"Naz","year":"2013","journal-title":"J. Nanobiotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ejps.2016.04.029","article-title":"PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility","volume":"91","author":"Muhammad","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Riaz, S., Rana, N.F., Hussain, I., Tanweer, T., Nawaz, A., Menaa, F., Janjua, H.A., Alam, T., Batool, A., and Naeem, A. (2020). Effect of Flavonoid-Coated Gold Nanoparticles on Bacterial Colonization in Mice Organs. Nanomaterials, 10.","DOI":"10.3390\/nano10091769"},{"key":"ref_37","first-page":"4","article-title":"Application of UV spectrophotometric methods for estimation of Ciprofloxacin and tinidazole in combined tablet dosage form","volume":"4","author":"Bhalerao","year":"2012","journal-title":"Int. J. Pharmacol. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jconrel.2016.06.017","article-title":"DLS and zeta potential\u2014What they are and what they are not?","volume":"235","author":"Bhattacharjee","year":"2016","journal-title":"J Control. Release"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-80953-3","article-title":"Non-disruptive uptake of anionic and cationic gold nanoparticles in neutral zwitterionic membranes","volume":"11","author":"Canepa","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111312","DOI":"10.1016\/j.colsurfb.2020.111312","article-title":"Gold nanoparticles-biomembrane interactions: From fundamental to simulation","volume":"196","author":"Okoampah","year":"2020","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4155\/tde.12.21","article-title":"Size matters: Gold nanoparticles in targeted cancer drug delivery","volume":"3","author":"Dreaden","year":"2012","journal-title":"Ther. Deliv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1081\/JDI-120022557","article-title":"Ciprofloxacin-Induced Acute Interstitial Nephritis and Autoimmune Hemolytic Anemia","volume":"25","author":"Lim","year":"2003","journal-title":"Ren. Fail."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/11\/3152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:33:53Z","timestamp":1760168033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/11\/3152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,22]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nano11113152"],"URL":"https:\/\/doi.org\/10.3390\/nano11113152","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,22]]}}}