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Volume 14
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Article

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

by
Wed Alluhaim
1,2,†,
Manal M. Alkhulaifi
1,*,†,
Raghad R. Alzahrani
1,2,
Bahauddeen M. Alrfaei
3,
Alaa Eldeen B. Yassin
4,
Majed F. Alghoribi
5,
Ahlam M. Alsaadi
5,
Ahmed I. Al-Asmari
6,7,
Ahmed J. Al-Fahad
8,
Rizwan Ali
9,
Naif M. Alhawiti
10 and
Majed A. Halwani
2,*
1
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
2
Nanomedicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
3
Stem Cells and Regenerative Medicine, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
4
College of Pharmacy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
5
Infectious Diseases Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
6
Special Toxicological Analysis Section, Pathology and Laboratory Department, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
7
Faculty of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
8
National Center for Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 12354, Saudi Arabia
9
Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
10
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
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antibiotics 2025, 14(1), 3; https://doi.org/10.3390/antibiotics14010003
Submission received: 28 October 2024 / Revised: 3 December 2024 / Accepted: 18 December 2024 / Published: 24 December 2024
(This article belongs to the Special Issue Strategies to Combat Antibiotic Resistance and Microbial Biofilms)
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Abstract

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 µg/mL, reduced the biofilm formation of the P. aeruginosa isolate (PA85) by 68%. Conversely, free TOB, at a MIC of 64 µg/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 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. 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.
Keywords: liposomes; manuka honey; methylglyoxal; tobramycin; biofilm liposomes; manuka honey; methylglyoxal; tobramycin; biofilm

Share and Cite

MDPI and ACS Style

Alluhaim, W.; Alkhulaifi, M.M.; Alzahrani, R.R.; Alrfaei, B.M.; Yassin, A.E.B.; Alghoribi, M.F.; Alsaadi, A.M.; Al-Asmari, A.I.; Al-Fahad, A.J.; Ali, R.; et al. Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion. Antibiotics 2025, 14, 3. https://doi.org/10.3390/antibiotics14010003

AMA Style

Alluhaim W, Alkhulaifi MM, Alzahrani RR, Alrfaei BM, Yassin AEB, Alghoribi MF, Alsaadi AM, Al-Asmari AI, Al-Fahad AJ, Ali R, et al. Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion. Antibiotics. 2025; 14(1):3. https://doi.org/10.3390/antibiotics14010003

Chicago/Turabian Style

Alluhaim, Wed, 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, and et al. 2025. "Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion" Antibiotics 14, no. 1: 3. https://doi.org/10.3390/antibiotics14010003

APA Style

Alluhaim, W., Alkhulaifi, M. M., Alzahrani, R. R., Alrfaei, B. M., Yassin, A. E. B., Alghoribi, M. F., Alsaadi, A. M., Al-Asmari, A. I., Al-Fahad, A. J., Ali, R., Alhawiti, N. M., & Halwani, M. A. (2025). Effectiveness of a Novel Liposomal Methylglyoxal–Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion. Antibiotics, 14(1), 3. https://doi.org/10.3390/antibiotics14010003

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