Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion

<b>Background:</b> 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 (...

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Main Authors: Wed Alluhaim, Manal M. Alkhulaifi, Raghad R. Alzahrani, Bahauddeen M. Alrfaei, Alaa Eldeen B. Yassin, Majed F. Alghoribi, Ahlam M. Alsaadi, Ahmed I. Al-Asmari, Ahmed J. Al-Fahad, Rizwan Ali, Naif M. Alhawiti, Majed A. Halwani
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Language:English
Published: MDPI AG 2024-12-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/1/3
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author Wed Alluhaim
Manal M. Alkhulaifi
Raghad R. Alzahrani
Bahauddeen M. Alrfaei
Alaa Eldeen B. Yassin
Majed F. Alghoribi
Ahlam M. Alsaadi
Ahmed I. Al-Asmari
Ahmed J. Al-Fahad
Rizwan Ali
Naif M. Alhawiti
Majed A. Halwani
author_facet Wed Alluhaim
Manal M. Alkhulaifi
Raghad R. Alzahrani
Bahauddeen M. Alrfaei
Alaa Eldeen B. Yassin
Majed F. Alghoribi
Ahlam M. Alsaadi
Ahmed I. Al-Asmari
Ahmed J. Al-Fahad
Rizwan Ali
Naif M. Alhawiti
Majed A. Halwani
author_sort Wed Alluhaim
collection DOAJ
description <b>Background:</b> 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. <b>Methods:</b> Clinical isolates of <i>Pseudomonas aeruginosa</i> and <i>Klebsiella pneumoniae</i> 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. <b>Results:</b> The Lip-MGO-TOB formulation, at a minimum inhibitory concentration (MIC) of 32 µg/mL, reduced the biofilm formation of the <i>P. aeruginosa</i> isolate (PA85) by 68%. Conversely, free TOB, at a MIC of 64 µg/mL, achieved only a 21% reduction. For the <i>K. pneumoniae</i> isolate (KP57), Lip-MGO-TOB inhibited bacterial adhesion to A549 cells at a lower concentration (256 µg/mL) compared to free TOB (512 µg/mL). Lip-MGO-TOB demonstrated sustained drug release over 24 h under tested conditions and retained over 99% of TOB. <b>Conclusions:</b> 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.
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spelling doaj-art-9898023f19434d52af90c88ccd5485662025-01-24T13:18:28ZengMDPI AGAntibiotics2079-63822024-12-01141310.3390/antibiotics14010003Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial AdhesionWed Alluhaim0Manal M. Alkhulaifi1Raghad R. Alzahrani2Bahauddeen M. Alrfaei3Alaa Eldeen B. Yassin4Majed F. Alghoribi5Ahlam M. Alsaadi6Ahmed I. Al-Asmari7Ahmed J. Al-Fahad8Rizwan Ali9Naif M. Alhawiti10Majed A. Halwani11Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaStem Cells and Regenerative Medicine, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaCollege of Pharmacy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaInfectious Diseases Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaInfectious Diseases Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaSpecial Toxicological Analysis Section, Pathology and Laboratory Department, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi ArabiaNational Center for Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi ArabiaMedical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaDepartment 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 ArabiaNanomedicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia<b>Background:</b> 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. <b>Methods:</b> Clinical isolates of <i>Pseudomonas aeruginosa</i> and <i>Klebsiella pneumoniae</i> 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. <b>Results:</b> The Lip-MGO-TOB formulation, at a minimum inhibitory concentration (MIC) of 32 µg/mL, reduced the biofilm formation of the <i>P. aeruginosa</i> isolate (PA85) by 68%. Conversely, free TOB, at a MIC of 64 µg/mL, achieved only a 21% reduction. For the <i>K. pneumoniae</i> isolate (KP57), Lip-MGO-TOB inhibited bacterial adhesion to A549 cells at a lower concentration (256 µg/mL) compared to free TOB (512 µg/mL). Lip-MGO-TOB demonstrated sustained drug release over 24 h under tested conditions and retained over 99% of TOB. <b>Conclusions:</b> 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.https://www.mdpi.com/2079-6382/14/1/3liposomesmanuka honeymethylglyoxaltobramycinbiofilm
spellingShingle Wed Alluhaim
Manal M. Alkhulaifi
Raghad R. Alzahrani
Bahauddeen M. Alrfaei
Alaa Eldeen B. Yassin
Majed F. Alghoribi
Ahlam M. Alsaadi
Ahmed I. Al-Asmari
Ahmed J. Al-Fahad
Rizwan Ali
Naif M. Alhawiti
Majed A. Halwani
Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion
Antibiotics
liposomes
manuka honey
methylglyoxal
tobramycin
biofilm
title Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion
title_full Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion
title_fullStr Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion
title_full_unstemmed Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion
title_short Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion
title_sort effectiveness of a novel liposomal methylglyoxal tobramycin formulation in reducing biofilm formation and bacterial adhesion
topic liposomes
manuka honey
methylglyoxal
tobramycin
biofilm
url https://www.mdpi.com/2079-6382/14/1/3
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