{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:43:26Z","timestamp":1785548606934,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh, Saudi Arabia","award":["RC20\/109\/R"],"award-info":[{"award-number":["RC20\/109\/R"]}]},{"name":"King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh, Saudi Arabia","award":["8789"],"award-info":[{"award-number":["8789"]}]},{"name":"Department of Botany and Microbiology at King Saud University","award":["RC20\/109\/R"],"award-info":[{"award-number":["RC20\/109\/R"]}]},{"name":"Department of Botany and Microbiology at King Saud University","award":["8789"],"award-info":[{"award-number":["8789"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The emergence of multidrug-resistant bacteria presents a significant global health threat. Liposomal antibiotics have shown a potential to improve antibiotic delivery and efficacy. This study aimed to develop liposomes encapsulating tobramycin (TOB) and methylglyoxal (MGO) to enhance TOB activity while reducing bacterial adhesion and biofilm formation. Methods: Clinical isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae were characterized using whole-genome sequencing. Liposomes (Lip-MGO-TOB) were formulated using Manuka honey as a surfactant and loaded with MGO and TOB. Antibacterial activity, biofilm formation, and bacterial cell adhesion assays were performed to compare the efficacy of Lip-MGO-TOB against free TOB. Liposome characterization included analyses of morphology, zeta potential, TOB encapsulation efficiency, and stability under various biological conditions. Results: The Lip-MGO-TOB formulation, at a minimum inhibitory concentration (MIC) of 32 \u00b5g\/mL, reduced the biofilm formation of the P. aeruginosa isolate (PA85) by 68%. Conversely, free TOB, at a MIC of 64 \u00b5g\/mL, achieved only a 21% reduction. For the K. pneumoniae isolate (KP57), Lip-MGO-TOB inhibited bacterial adhesion to A549 cells at a lower concentration (256 \u00b5g\/mL) compared to free TOB (512 \u00b5g\/mL). Lip-MGO-TOB demonstrated sustained drug release over 24 h under tested conditions and retained over 99% of TOB. Conclusions: The Lip-MGO-TOB formulation significantly enhanced TOB activity against resistant bacteria compared to free TOB. Additionally, it provided a stable drug delivery system with controlled drug release. Liposomal TOB represents a promising advancement in combating antibiotic resistance by improving the efficacy and delivery of conventional antibiotics.<\/jats:p>","DOI":"10.3390\/antibiotics14010003","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T09:00:57Z","timestamp":1735030857000},"page":"3","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effectiveness of a Novel Liposomal Methylglyoxal\u2013Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7345-1028","authenticated-orcid":false,"given":"Wed","family":"Alluhaim","sequence":"first","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Nanomedicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5040-6303","authenticated-orcid":false,"given":"Manal M.","family":"Alkhulaifi","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0617-7929","authenticated-orcid":false,"given":"Raghad R.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Nanomedicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5740-9187","authenticated-orcid":false,"given":"Bahauddeen M.","family":"Alrfaei","sequence":"additional","affiliation":[{"name":"Stem Cells and Regenerative Medicine, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3532-7583","authenticated-orcid":false,"given":"Alaa Eldeen B.","family":"Yassin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2122-8640","authenticated-orcid":false,"given":"Majed F.","family":"Alghoribi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-1180","authenticated-orcid":false,"given":"Ahlam M.","family":"Alsaadi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-2194","authenticated-orcid":false,"given":"Ahmed I.","family":"Al-Asmari","sequence":"additional","affiliation":[{"name":"Special Toxicological Analysis Section, Pathology and Laboratory Department, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"},{"name":"Faculty of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed J.","family":"Al-Fahad","sequence":"additional","affiliation":[{"name":"National Center for Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2475-0258","authenticated-orcid":false,"given":"Rizwan","family":"Ali","sequence":"additional","affiliation":[{"name":"Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8357-6886","authenticated-orcid":false,"given":"Naif M.","family":"Alhawiti","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, King Abdullah International Medical Research Center, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2192-3264","authenticated-orcid":false,"given":"Majed A.","family":"Halwani","sequence":"additional","affiliation":[{"name":"Nanomedicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.mib.2019.10.008","article-title":"Antibiotics: Past, present and future","volume":"51","author":"Hutchings","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Thy, M., Timsit, J.F., and de Montmollin, E. (2023). Aminoglycosides for the treatment of severe infection due to resistant gram-negative pathogens. Antibiotics, 12.","DOI":"10.3390\/antibiotics12050860"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Salam, M.A., Al-Amin, M.Y., Salam, M.T., Pawar, J.S., Akhter, N., Rabaan, A.A., and Alqumber, M.A.A. (2023). Antimicrobial resistance: A growing serious threat for global public health. Healthcare, 11.","DOI":"10.20944\/preprints202305.0555.v1"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Baptista, P.V., McCusker, M.P., Carvalho, A., Ferreira, D.A., Mohan, N.M., Martins, M., and Fernandes, A.R. (2018). Nano-strategies to fight multidrug-resistant bacteria: \u201cA battle of the titans\u201d. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01441"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ferreira, M., Ogren, M., Dias, J.N.R., Silva, M., Gil, S., Tavares, L., Aires-Da-Silva, F., Gaspar, M.M., and Aguiar, S.I. (2021). Liposomes as antibiotic delivery systems: A promising nanotechnological strategy against antimicrobial resistance. Molecules, 26.","DOI":"10.3390\/molecules26072047"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rukavina, Z., and Vani\u0107, \u017d. (2016). Current trends in development of liposomes for targeting bacterial biofilms. Pharmaceutics, 8.","DOI":"10.3390\/pharmaceutics8020018"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ijpharm.2009.11.033","article-title":"Liposomes as delivery systems for antibiotics","volume":"387","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1701400","DOI":"10.1002\/adhm.201701400","article-title":"Recent advances in the development of antimicrobial nanoparticles for combating resistant pathogens","volume":"7","author":"Lakshminarayanan","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.tvjl.2012.01.002","article-title":"Nanomedicine and veterinary science: The reality and the practicality","volume":"193","author":"Underwood","year":"2012","journal-title":"Vet. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bahari, N., Hashim, N., Md Akim, A., and Maringgal, B. (2022). Recent advances in honey-based nanoparticles for wound dressing: A review. Nanomaterials, 12.","DOI":"10.3390\/nano12152560"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3934\/microbiol.2018.4.655","article-title":"Antibacterial activity of Manuka honey and its components: An overview","volume":"4","author":"Johnston","year":"2018","journal-title":"AIMS Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3390\/foods3030420","article-title":"The composition and biological activity of honey: A focus on manuka honey","volume":"3","author":"Gasparrini","year":"2014","journal-title":"Foods"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Brudzynski, K. (2021). Honey as an ecological reservoir of antibacterial compounds produced by antagonistic microbial interactions in plant nectars, honey and honey bee. Antibiotics, 10.","DOI":"10.3390\/antibiotics10050551"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.17221\/911-CJFS","article-title":"Methylglyoxal in Manuka honey: Correlation with antibacterial properties","volume":"27","author":"Atrott","year":"2009","journal-title":"Czech J. Food Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1042\/bst0311406","article-title":"Bacterial production of methylglyoxal: A survival strategy or death by misadventure?","volume":"31","author":"Booth","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.carres.2012.07.025","article-title":"Studies on the formation of methylglyoxal from dihydroxyacetone in Manuka (Leptospermum scoparium) honey","volume":"361","author":"Atrott","year":"2012","journal-title":"Carbohydr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1017\/S0007114509992777","article-title":"Demonstrating the safety of manuka honey UMF 20+ in a human clinical trial with healthy individuals","volume":"103","author":"Wallace","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_18","first-page":"121","article-title":"Honey and health: A review of recent clinical research","volume":"9","author":"Samarghandian","year":"2017","journal-title":"Pharmacogn. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1517\/17425247.2012.717927","article-title":"Nanotechnology for targeted drug delivery to combat antibiotic resistance","volume":"9","author":"Sharma","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1080\/10717544.2016.1177136","article-title":"Pharmaceutical liposomal drug delivery: A review of new delivery systems and a look at the regulatory landscape","volume":"23","author":"Zylberberg","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.15171\/apb.2016.021","article-title":"The impact of variables on particle size of solid lipid nanoparticles and nanostructured lipid carriers: A comparative literature review","volume":"6","author":"Bahari","year":"2016","journal-title":"Adv. Pharm. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/1381612820666140905123529","article-title":"Strategies for antimicrobial drug delivery to biofilm","volume":"21","author":"Martin","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., Khorasani, S., and Mozafari, M.R. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020057"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3109\/10717541003762870","article-title":"Liposome combined porous \u03b2-TCP scaffold: Preparation, characterization, and anti-biofilm activity","volume":"17","author":"Zhu","year":"2010","journal-title":"Drug Deliv."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Leong, E.W.X., and Ge, R. (2022). Lipid nanoparticles as delivery vehicles for inhaled therapeutics. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092179"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1165\/rcmb.2020-0306TR","article-title":"Nanoparticle delivery systems with cell-specific targeting for pulmonary diseases","volume":"64","author":"Deng","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113862","DOI":"10.1016\/j.cattod.2022.08.004","article-title":"Zeta potential as a tool for functional materials development","volume":"423","author":"Portela","year":"2023","journal-title":"Catal. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101057","DOI":"10.1016\/j.fochx.2023.101057","article-title":"Enhancement of liposomal properties of thyme essential oil using lysozyme modification: Physicochemical, storage, and antibacterial properties","volume":"20","author":"Zhou","year":"2023","journal-title":"Food Chem. X"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/10717540490265243","article-title":"The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations","volume":"11","author":"Anderson","year":"2004","journal-title":"Drug Deliv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e79220","DOI":"10.1371\/journal.pone.0079220","article-title":"Transport of nanoparticles and tobramycin-loaded liposomes in Burkholderia cepacia complex biofilms","volume":"8","author":"Messiaen","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/CMR.00117-14","article-title":"The challenge of efflux-mediated antibiotic resistance in gram-negative bacteria","volume":"28","author":"Li","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1099\/mic.0.001322","article-title":"Drug resistance and physiological roles of RND multidrug efflux pumps in Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa","volume":"169","author":"Yamasaki","year":"2023","journal-title":"Microbiology"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nikaido, H. (2014). Role, structure, and function of multidrug efflux pumps in gram-negative bacteria. Frontiers in Antimicrobial Resistance, ASM Press.","DOI":"10.1128\/9781555817572.ch19"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Avakh, A., Grant, G.D., Cheesman, M.J., Kalkundri, T., and Hall, S. (2023). The art of war with Pseudomonas aeruginosa: Targeting Mex efflux pumps directly to strategically enhance antipseudomonal drug efficacy. Antibiotics, 12.","DOI":"10.3390\/antibiotics12081304"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/j.1574-6976.2008.00157.x","article-title":"Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems","volume":"33","author":"Martinez","year":"2009","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e23368","DOI":"10.1016\/j.heliyon.2023.e23368","article-title":"Resistance to aminoglycoside and quinolone drugs among Klebsiella pneumoniae clinical isolates from northern Jordan","volume":"10","author":"Swedan","year":"2024","journal-title":"Heliyon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1099\/mic.0.001237","article-title":"In vitro synergy between manuka honey and amikacin against Mycobacterium abscessus complex shows potential for nebulisation therapy","volume":"168","author":"Nolan","year":"2022","journal-title":"Microbiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fmicb.2014.00180","article-title":"Effect of methylglyoxal on multidrug-resistant Pseudomonas aeruginosa","volume":"5","author":"Hayashi","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3109\/01913123.2016.1154914","article-title":"How methylglyoxal kills bacteria: An ultrastructural study","volume":"40","author":"Rabie","year":"2016","journal-title":"Ultrastruct. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1128\/AAC.45.5.1487-1492.2001","article-title":"Improved efficacy of ciprofloxacin administered in polyethylene glycol-coated liposomes for treatment of Klebsiella pneumoniae pneumonia in rats","volume":"45","author":"Guo","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","first-page":"360","article-title":"A comparison of the in vitro antimicrobial activity of liposomes containing meropenem and gentamicin","volume":"11","author":"Gubernator","year":"2006","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liu, P., Chen, G., and Zhang, J. (2022). A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules, 27.","DOI":"10.3390\/molecules27041372"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35442","DOI":"10.1021\/acsomega.3c04893","article-title":"Liposome-based antibacterial delivery: An emergent approach to combat bacterial infections","volume":"8","author":"Ghosh","year":"2023","journal-title":"ACS Omega"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e0160741","DOI":"10.1371\/journal.pone.0160741","article-title":"Burkholderia pseudomallei biofilm promotes adhesion, internalization, and stimulates proinflammatory cytokines in human epithelial A549 cells","volume":"11","author":"Kunyanee","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8298","DOI":"10.1128\/IAI.73.12.8298-8305.2005","article-title":"Pseudomonas aeruginosa acquires biofilm-like properties within airway epithelial cells","volume":"73","author":"Dunne","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_46","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_47","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_48","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_49","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Khan, S., Kazi, M., Alshehri, S.M., Shahid, M., Khan, S.U., Hussain, Z., Sohail, M., Shafique, M., and Hamid, H.A. (2021). Norfloxacin-loaded lipid polymer hybrid nanoparticles for oral administration: Fabrication, characterization, in silico modeling, and toxicity evaluation. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101632"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2147\/IJN.S14615","article-title":"AFM, ESEM, TEM, and CLSM in liposomal characterization: A comparative study","volume":"6","author":"Ruozi","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Alarfaj, R.E., Alkhulaifi, M.M., Al-Fahad, A.J., Aljihani, S., Yassin, A.E.B., Alghoribi, M.F., and Halwani, M.A. (2022). Antibacterial efficacy of liposomal formulations containing tobramycin and N-acetylcysteine against tobramycin-resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010130"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"736","DOI":"10.5897\/AJMR2018.8893","article-title":"Low accuracy of the McFarland method for estimation of bacterial populations","volume":"12","author":"Eduardo","year":"2018","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_53","unstructured":"EUCAST\/ESCMID (2003). EUCAST discussion document E. Dis 5.1 March 2003: Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution. Clin. Microbiol. Infect., 9, 1\u20137."},{"key":"ref_54","unstructured":"CLSI (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically: Approved Guideline M07, Clinical and Laboratory Standards Institute. [11th ed.]."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.phymed.2011.11.010","article-title":"Synergistic activity of coriander oil and conventional antibiotics against Acinetobacter baumannii","volume":"19","author":"Duarte","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s42269-019-0131-9","article-title":"Determination of optimum incubation time for formation of Pseudomonas aeruginosa and Streptococcus pyogenes biofilms in microtiter plate","volume":"43","author":"Bakar","year":"2019","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.1128\/iai.64.10.4054-4059.1996","article-title":"Invasion of respiratory epithelial cells by Burkholderia (Pseudomonas) cepacia","volume":"64","author":"Burns","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.tim.2003.08.006","article-title":"Multi-locus sequence typing: A tool for global epidemiology","volume":"11","author":"Urwin","year":"2003","journal-title":"Trends Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"D561","DOI":"10.1093\/nar\/gkz1010","article-title":"MEGARes 2.0: A database for classification of antimicrobial drug, biocide, and metal resistance determinants in metagenomic sequence data","volume":"48","author":"Doster","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1093\/jac\/dks261","article-title":"Identification of acquired antimicrobial resistance genes","volume":"67","author":"Zankari","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1128\/JB.182.6.1754-1756.2000","article-title":"AcrD of Escherichia coli is an aminoglycoside efflux pump","volume":"182","author":"Rosenberg","year":"2000","journal-title":"J. Bacteriol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/1\/3\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:59:04Z","timestamp":1760115544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/1\/3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,24]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["antibiotics14010003"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14010003","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,24]]}}}