{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:09:53Z","timestamp":1791846593031,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T00:00:00Z","timestamp":1618704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laurentian University Research Fund (LURF)","award":["2018"],"award-info":[{"award-number":["2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The eradication of Pseudomonas aeruginosa in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, against P. aeruginosa isolates. Liposomes were prepared and characterized for their sizes and encapsulation efficiencies. The antimicrobial activities of formulations were determined by the microbroth dilution method. Their activity on P. aeruginosa biofilms was assessed, and the effect of sub-inhibitory concentrations on bacterial virulence factors, quorum sensing (QS) signals and bacterial motility was also evaluated. The average diameters of liposomes were 562.67 \u00b1 33.74 nm for gentamicin and 3086.35 \u00b1 553.95 nm for erythromycin, with encapsulation efficiencies of 13.89 \u00b1 1.54% and 51.58 \u00b1 2.84%, respectively. Liposomes and PABN combinations potentiated antibiotics by reducing minimum inhibitory and bactericidal concentrations by 4\u201332 fold overall. The formulations significantly inhibited biofilm formation and differentially attenuated virulence factor production as well as motility. Unexpectedly, QS signal production was not affected by treatments. Taken together, the results indicate that PABN shows potential as an adjuvant of liposomal macrolides and aminoglycosides in the management of lung infections in cystic fibrosis patients.<\/jats:p>","DOI":"10.3390\/pharmaceutics13040577","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T06:35:53Z","timestamp":1618814153000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa"],"prefix":"10.3390","volume":"13","author":[{"given":"Douweh Leyla","family":"Gbian","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Novel Drug and Vaccine Delivery Systems Facility, Laurentian University, Sudbury, ON P3E 2C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4093-5762","authenticated-orcid":false,"given":"Abdelwahab","family":"Omri","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Novel Drug and Vaccine Delivery Systems Facility, Laurentian University, Sudbury, ON P3E 2C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.jcf.2019.04.009","article-title":"Mucoid Pseudomonas Aeruginosa and Regional Inflammation in the Cystic Fibrosis Lung","volume":"18","author":"Malhotra","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_2","first-page":"4053","article-title":"Gentamicin-Loaded Nanoparticles Show Improved Antimicrobial Effects towards Pseudomonas Aeruginosa Infection","volume":"7","author":"Abdelghany","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1007\/s00253-015-7177-x","article-title":"The Cystic Fibrosis Microbiome in an Ecological Perspective and Its Impact in Antibiotic Therapy","volume":"100","author":"Azevedo","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e02583-17","DOI":"10.1128\/AAC.02583-17","article-title":"Evolution of the Pseudomonas Aeruginosa Aminoglycoside Mutational Resistome In Vitro and in the Cystic Fibrosis Setting","volume":"62","author":"Rubio","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.ijantimicag.2018.11.001","article-title":"Ceftolozane\/Tazobactam for the Treatment of Serious Pseudomonas Aeruginosa Infections: A Multicentre Nationwide Clinical Experience","volume":"53","author":"Bassetti","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/jac\/dky546","article-title":"In Vitro Activity of Apramycin against Multidrug-, Carbapenem- and Aminoglycoside-Resistant Enterobacteriaceae and Acinetobacter Baumannii","volume":"74","author":"Juhas","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104249","DOI":"10.1016\/j.micpath.2020.104249","article-title":"Inhibition of Biofilm and Virulence Properties of Pseudomonas Aeruginosa by Sub-Inhibitory Concentrations of Aminoglycosides","volume":"146","author":"Khan","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1007\/s00253-019-10288-1","article-title":"A Putative Mechanism Underlying Secondary Metabolite Overproduction by Streptomyces Strains with a 23S RRNA Mutation Conferring Erythromycin Resistance","volume":"104","author":"Hoshino","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S2213-2600(19)30191-2","article-title":"Long-Term Macrolide Antibiotics for the Treatment of Bronchiectasis in Adults: An Individual Participant Data Meta-Analysis","volume":"7","author":"Chalmers","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1164\/rccm.201802-0215OC","article-title":"Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial","volume":"198","author":"Kloster","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jconrel.2019.10.038","article-title":"Spray-Drying of Inhalable, Multifunctional Formulations for the Treatment of Biofilms Formed in Cystic Fibrosis","volume":"314","author":"Lababidi","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.ijpharm.2014.05.055","article-title":"Spray Dried Amikacin Powder for Inhalation in Cystic Fibrosis Patients: A Quality by Design Approach for Product Construction","volume":"471","author":"Belotti","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11414-3","article-title":"Genetically Diverse Pseudomonas Aeruginosa Populations Display Similar Transcriptomic Profiles in a Cystic Fibrosis Explanted Lung","volume":"10","author":"Kordes","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.3389\/fmicb.2020.01001","article-title":"Distinctive Regulation of Carbapenem Susceptibility in Pseudomonas Aeruginosa by Hfq","volume":"11","author":"Sonnleitner","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Abbasi, F., Yusefi, S., and Yavar, S.A. (2018). Minimum Inhibitory Concentration of Ciprofloxacin against Pseudomonas Aeruginosa in the Presence of the Efflux Inhibitor Phenylalanine-Arginine Beta-Naphthylamide. Intern. Med. Med. Investig. J., 3.","DOI":"10.24200\/imminv.v2i4.128"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.drup.2016.11.002","article-title":"Active Efflux in Dormant Bacterial Cells \u2013 New Insights into Antibiotic Persistence","volume":"30","author":"Pu","year":"2017","journal-title":"Drug Resist. Updat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.biotechadv.2018.11.013","article-title":"Antibiotic Resistance in Pseudomonas Aeruginosa: Mechanisms and Alternative Therapeutic Strategies","volume":"37","author":"Pang","year":"2019","journal-title":"Biotechnol. Adv."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sans-Serramitjana, E., Jorba, M., Fust\u00e9, E., Pedraz, J.L., Vinuesa, T., and Vi\u00f1as, M. (2017). Free and Nanoencapsulated Tobramycin: Effects on Planktonic and Biofilm Forms of Pseudomonas. Microorganisms, 5.","DOI":"10.3390\/microorganisms5030035"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e01081-19","DOI":"10.1128\/AAC.01081-19","article-title":"Cinnamaldehyde Induces Expression of Efflux Pumps and Multidrug Resistance in Pseudomonas Aeruginosa","volume":"63","author":"Tetard","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","first-page":"32","article-title":"Mutations in Nalc Gene of Mex AB-OprM Efflux Pump in Carbapenem Resistant Pseudomonas Aeruginosa Isolated from Burn Wounds in Yazd, Iran","volume":"12","author":"Tafti","year":"2020","journal-title":"Iran J. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Minagawa, S., Inami, H., Kato, T., Sawada, S., Yasuki, T., Miyairi, S., Horikawa, M., Okuda, J., and Gotoh, N. (2012). RND Type Efflux Pump System MexAB-OprM of Pseudomonas Aeruginosa Selects Bacterial Languages, 3-Oxo-Acyl-Homoserine Lactones, for Cell-to-Cell Communication. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-70"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1099\/mic.0.000971","article-title":"MexXY RND Pump of Pseudomonas Aeruginosa PA7 Effluxes Bi-Anionic \u03b2-Lactams Carbenicillin and Sulbenicillin When It Partners with the Outer Membrane Factor OprA but Not with OprM","volume":"166","author":"Singh","year":"2020","journal-title":"Microbiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e01166-20","DOI":"10.1128\/AAC.01166-20","article-title":"Expression of the MexXY Aminoglycoside Efflux Pump and Presence of an Aminoglycoside-Modifying Enzyme in Clinical Pseudomonas Aeruginosa Isolates Are Highly Correlated","volume":"65","author":"Seupt","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e02033-19","DOI":"10.1128\/AAC.02033-19","article-title":"The Efflux Pump MexXY\/OprM Contributes to the Tolerance and Acquired Resistance of Pseudomonas Aeruginosa to Colistin","volume":"64","author":"Puja","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00532-20","DOI":"10.1128\/mBio.00532-20","article-title":"RhlR-Regulated Acyl-Homoserine Lactone Quorum Sensing in a Cystic Fibrosis Isolate of Pseudomonas Aeruginosa","volume":"11","author":"Cruz","year":"2020","journal-title":"mBio"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1007\/s00248-017-0949-3","article-title":"Reducing Virulence and Biofilm of Pseudomonas Aeruginosa by Potential Quorum Sensing Inhibitor Carotenoid: Zeaxanthin","volume":"74","author":"Aksoydan","year":"2017","journal-title":"Microb. Ecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104412","DOI":"10.1016\/j.micpath.2020.104412","article-title":"Terminalia Chebula and Ficus Racemosa Principles Mediated Repression of Novel Drug Target Las R\u2014The Transcriptional Regulator and Its Controlled Virulence Factors Produced by Multiple Drug Resistant Pseudomonas Aeruginosa\u2014Biocompatible Formulation against Drug Resistant Bacteria","volume":"148","author":"Angel","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s42770-020-00235-y","article-title":"Inhibition of Quorum Sensing\u2013Associated Virulence Factors and Biofilm Formation in Pseudomonas Aeruginosa PAO1 by Mycoleptodiscus Indicus PUTY1","volume":"51","author":"Ahmed","year":"2020","journal-title":"Braz. J. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.3389\/fmicb.2020.01668","article-title":"2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia Eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas Aeruginosa","volume":"11","author":"Mishra","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12951-020-0588-6","article-title":"Antibacterial Activity of Iron Oxide, Iron Nitride, and Tobramycin Conjugated Nanoparticles against Pseudomonas Aeruginosa Biofilms","volume":"18","author":"Armijo","year":"2020","journal-title":"J. Nanobiotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-56913-x","article-title":"Iron Acquisition in Pseudomonas Aeruginosa by the Siderophore Pyoverdine: An Intricate Interacting Network Including Periplasmic and Membrane Proteins","volume":"10","author":"Bonneau","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100024","DOI":"10.1016\/j.bioflm.2020.100024","article-title":"Building a Better Biofilm - Formation of in Vivo-like Biofilm Structures by Pseudomonas Aeruginosa in a Porcine Model of Cystic Fibrosis Lung Infection","volume":"2","author":"Harrington","year":"2020","journal-title":"Biofilm"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3389\/fmicb.2019.00570","article-title":"Social Behavior of Antibiotic Resistant Mutants Within Pseudomonas Aeruginosa Biofilm Communities","volume":"10","author":"Oliver","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17981","DOI":"10.1073\/pnas.1316981110","article-title":"A Quorum-Sensing Inhibitor Blocks Pseudomonas Aeruginosa Virulence and Biofilm Formation","volume":"110","author":"Miller","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-36488-9","article-title":"Quorum Sensing in Pseudomonas Aeruginosa Mediated by RhlR Is Regulated by a Small RNA PhrD","volume":"9","author":"Malgaonkar","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jtcme.2017.05.008","article-title":"Attenuation of Quorum-Sensing-Dependent Virulence Factors and Biofilm Formation by Medicinal Plants against Antibiotic Resistant Pseudomonas Aeruginosa","volume":"8","year":"2018","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.2353\/ajpath.2009.090166","article-title":"Pseudomonas Aeruginosa Exotoxin Pyocyanin Causes Cystic Fibrosis Airway Pathogenesis","volume":"175","author":"Caldwell","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1089\/ars.2014.5979","article-title":"Pseudomonas Aeruginosa Pyocyanin Induces Neutrophil Death via Mitochondrial Reactive Oxygen Species and Mitochondrial Acid Sphingomyelinase","volume":"22","author":"Becker","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41579-018-0048-6","article-title":"Multidrug Efflux Pumps: Structure, Function and Regulation","volume":"16","author":"Du","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.3389\/fmicb.2018.03317","article-title":"Novel Pyoverdine Inhibitors Mitigate Pseudomonas Aeruginosa Pathogenesis","volume":"9","author":"Kirienko","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kishk, R.M., Abdalla, M.O., Hashish, A.A., Nemr, N.A., El Nahhas, N., Alkahtani, S., Abdel-Daim, M.M., and Kishk, S.M. (2020). Efflux MexAB-Mediated Resistance in P. Aeruginosa Isolated from Patients with Healthcare Associated Infections. Pathogens, 9.","DOI":"10.3390\/pathogens9060471"},{"key":"ref_42","first-page":"1","article-title":"A Permeability-Increasing Drug Synergizes with Bacterial Efflux Pump Inhibitors and Restores Susceptibility to Antibiotics in Multi-Drug Resistant Pseudomonas Aeruginosa Strains","volume":"9","author":"Shahrour","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1099\/jmm.0.000327","article-title":"Control of Quorum Sensing and Virulence Factors of Pseudomonas Aeruginosa Using Phenylalanine Arginyl \u03b2-Naphthylamide","volume":"65","author":"Shaaban","year":"2016","journal-title":"J. Med. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lamers, R.P., Cavallari, J.F., and Burrows, L.L. (2013). The Efflux Inhibitor Phenylalanine-Arginine Beta-Naphthylamide (PA\u03b2N) Permeabilizes the Outer Membrane of Gram-Negative Bacteria. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060666"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.chemphyslip.2017.12.007","article-title":"Novel Lipids with Three C18-Fatty Acid Chains and an Amino Acid Head Group for PH-Responsive and Sustained Antibiotic Delivery","volume":"212","author":"Jadhav","year":"2018","journal-title":"Chem. Phys. Lipids"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jconrel.2020.06.002","article-title":"Liposomal Delivery of Antibiotic Loaded Nucleic Acid Nanogels with Enhanced Drug Loading and Synergistic Anti-Inflammatory Activity against S. aureus Intracellular Infections","volume":"324","author":"Obuobi","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1128\/AAC.01634-12","article-title":"Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas Aeruginosa Infection","volume":"57","author":"Alhariri","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3389\/fmicb.2018.00915","article-title":"Amikacin Liposome Inhalation Suspension (ALIS) Penetrates Non-Tuberculous Mycobacterial Biofilms and Enhances Amikacin Uptake Into Macrophages","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Cipolla, D., Blanchard, J., and Gonda, I. (2016). Development of Liposomal Ciprofloxacin to Treat Lung Infections. Pharmaceutics, 8.","DOI":"10.3390\/pharmaceutics8010006"},{"key":"ref_50","first-page":"247","article-title":"Antibacterial Activity of Liposomal Gentamicin against Pseudomonas Aeruginosa: A Time\u2013Kill Study","volume":"27","author":"Rukholm","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1128\/AAC.00235-13","article-title":"Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas Aeruginosa Virulence Factors","volume":"57","author":"Alhajlan","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/jac\/dku452","article-title":"Antimicrobial Properties of Liposomal Azithromycin for Pseudomonas Infections in Cystic Fibrosis Patients","volume":"70","author":"Solleti","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ijpharm.2005.10.005","article-title":"Preparation and Characterization of Dehydration\u2013Rehydration Vesicles Loaded with Aminoglycoside and Macrolide Antibiotics","volume":"307","author":"Mugabe","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/jac\/dkn422","article-title":"Co-Encapsulation of Gallium with Gentamicin in Liposomes Enhances Antimicrobial Activity of Gentamicin against Pseudomonas Aeruginosa","volume":"62","author":"Halwani","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_55","unstructured":"(2021, April 17). Innovotech MBEC Assay\u00ae. Available online: https:\/\/www.innovotech.ca\/products\/mbec-assays\/."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1139\/y11-057","article-title":"Ginseng Aqueous Extract Attenuates the Production of Virulence Factors, Stimulates Twitching and Adhesion, and Eradicates Biofilms of Pseudomonas Aeruginosa","volume":"89","author":"Alipour","year":"2011","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1093\/jac\/dkq036","article-title":"Attenuation of Pseudomonas Aeruginosa Virulence Factors and Biofilms by Co-Encapsulation of Bismuth\u2013Ethanedithiol with Tobramycin in Liposomes","volume":"65","author":"Alipour","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.micpath.2017.01.015","article-title":"Bioavailability-Enhanced ResveramaxTM Modulates Quorum Sensing and Inhibits Biofilm Formation in Pseudomonas Aeruginosa PAO1","volume":"104","author":"Vasavi","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.micpath.2014.07.008","article-title":"Aspirin Is an Efficient Inhibitor of Quorum Sensing, Virulence and Toxins in Pseudomonas Aeruginosa","volume":"74","author":"Shaaban","year":"2014","journal-title":"Microb. Pathog."},{"key":"ref_60","unstructured":"Miller, J.H., and Miller, J.B. (1972). Experiments in Molecular Genetics, Cold Spring Harbor Laboratory. Bacterial genetics-E. coli."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1128\/AAC.01547-05","article-title":"Mechanism of Enhanced Activity of Liposome-Entrapped Aminoglycosides against Resistant Strains of Pseudomonas Aeruginosa","volume":"50","author":"Mugabe","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6949","DOI":"10.2147\/IJN.S141709","article-title":"Efficacy of Neutral and Negatively Charged Liposome-Loaded Gentamicin on Planktonic Bacteria and Biofilm Communities","volume":"12","author":"Alhariri","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/00914037.2018.1434651","article-title":"Influence of Probe-Sonication Process on Drug Entrapment Efficiency of Liposomes Loaded with a Hydrophobic Drug","volume":"68","author":"He","year":"2019","journal-title":"Int. J. Polym. Mater."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3109\/08982100903218892","article-title":"Characterization of the Interaction between Liposomal Formulations and Pseudomonas Aeruginosa","volume":"20","author":"Jia","year":"2010","journal-title":"J. Liposome Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ijpharm.2018.09.061","article-title":"Novel Combination Proliposomes Containing Tobramycin and Clarithromycin Effective against Pseudomonas Aeruginosa Biofilms","volume":"552","author":"Ye","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1021\/acs.molpharmaceut.6b00360","article-title":"Incorporation of Farnesol Significantly Increases the Efficacy of Liposomal Ciprofloxacin against Pseudomonas Aeruginosa Biofilms in Vitro","volume":"13","author":"Bandara","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12575-019-0106-0","article-title":"MBEC versus MBIC: The Lack of Differentiation between Biofilm Reducing and Inhibitory Effects as a Current Problem in Biofilm Methodology","volume":"21","author":"Thieme","year":"2019","journal-title":"Biol. Proced. Online"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1080\/21505594.2018.1489198","article-title":"Inhibition of Pseudomonas Aeruginosa Secreted Virulence Factors Reduces Lung Inflammation in CF Mice","volume":"9","author":"Sandri","year":"2018","journal-title":"Virulence"},{"key":"ref_69","first-page":"1697","article-title":"Macrolide Treatment Inhibits Pseudomonas Aeruginosa Quorum Sensing in Non\u2013Cystic Fibrosis Bronchiectasis. An Analysis from the Bronchiectasis and Low-Dose Erythromycin Study Trial","volume":"13","author":"Burr","year":"2016","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00253-019-10190-w","article-title":"Streptomycin Mediated Biofilm Inhibition and Suppression of Virulence Properties in Pseudomonas Aeruginosa PAO1","volume":"104","author":"Khan","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-11892-9","article-title":"Effect of Efflux Pump Inhibition on Pseudomonas Aeruginosa Transcriptome and Virulence","volume":"7","author":"Rampioni","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4103\/0971-5916.187114","article-title":"Subinhibitory Concentration of Ciprofloxacin Targets Quorum Sensing System of Pseudomonas Aeruginosa Causing Inhibition of Biofilm Formation & Reduction of Virulence","volume":"143","author":"Gupta","year":"2016","journal-title":"Indian J. Med. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.micpath.2018.05.042","article-title":"Quorum Sensing Signals and Related Virulence Inhibition of Pseudomonas Aeruginosa by a Potential Probiotic Strain\u2019s Organic Acid","volume":"121","author":"Kiymaci","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"199","DOI":"10.4314\/ahs.v17i1.25","article-title":"Quorum Sensing Inhibitory Activity of Sub-Inhibitory Concentrations of \u03b2-Lactams","volume":"17","author":"Galil","year":"2017","journal-title":"Afr. Health Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1128\/AAC.50.5.1680-1688.2006","article-title":"Quorum-Sensing Antagonistic Activities of Azithromycin in Pseudomonas Aeruginosa PAO1: A Global Approach","volume":"50","author":"Nalca","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_76","first-page":"2757","article-title":"Role of the Multidrug Resistance Efflux Pump MexCD-OprJ in the Pseudomonas Aeruginosa Quorum Sensing Response","volume":"9","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Lamarche, M.G., and D\u00e9ziel, E. (2011). MexEF-OprN Efflux Pump Exports the Pseudomonas Quinolone Signal (PQS) Precursor HHQ (4-Hydroxy-2-Heptylquinoline). PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024310"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1099\/mic.0.27631-0","article-title":"The MexGHI-OpmD Multidrug Efflux Pump Controls Growth, Antibiotic Susceptibility and Virulence in Pseudomonas Aeruginosa via 4-Quinolone-Dependent Cell-to-Cell Communication","volume":"151","author":"Aendekerk","year":"2005","journal-title":"Microbiology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/1462-2920.14985","article-title":"A Molecular Mechanism for How Sigma Factor AlgT and Transcriptional Regulator AmrZ Inhibit Twitching Motility in Pseudomonas Aeruginosa","volume":"23","author":"Xu","year":"2020","journal-title":"Environ. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Dave, A., Samarth, A., Karolia, R., Sharma, S., Karunakaran, E., Partridge, L., MacNeil, S., Monk, P.N., Garg, P., and Roy, S. (2020). Characterization of Ocular Clinical Isolates of Pseudomonas Aeruginosa from Non-Contact Lens Related Keratitis Patients from South India. Microorganisms, 8.","DOI":"10.3390\/microorganisms8020260"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1111\/jam.14563","article-title":"A Compound Isolated from Alpinia Officinarum Hance. Inhibits Swarming Motility of Pseudomonas Aeruginosa and down Regulates Virulence Genes","volume":"128","author":"Lakshmanan","year":"2020","journal-title":"J. Appl. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/BF01961867","article-title":"Inhibition of Motility of Pseudomonas Aeruginosa and Proteus Mirabilis by Subinhibitory Concentrations of Azithromycin","volume":"11","author":"Molinari","year":"1992","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jgar.2017.03.006","article-title":"Inhibition of Pseudomonas Aeruginosa Quorum Sensing by Subinhibitory Concentrations of Curcumin with Gentamicin and Azithromycin","volume":"10","author":"Bahari","year":"2017","journal-title":"J. Glob. Antimicrob. Resist."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/4\/577\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:30Z","timestamp":1760161770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/4\/577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,18]]},"references-count":83,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["pharmaceutics13040577"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13040577","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,18]]}}}