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Polymyxin B-loaded PVP-capped silver nanoparticles: A potent approach against multidrug-resistant bacteria
Mohammad Jaafreh1, Walhan Alshaer2, Mahmoud Y Alkawareek3
1Faculty of Pharmacy, Universiti Sultan Zainal Abidin, Besut Campus, Besut, 22200, Terengganu, Malaysia.
Abstract:
The rapid emergence of multidrug-resistant (MDR) bacteria poses a critical global health threat, severely limiting the effectiveness of current antibiotics. Polymyxin B (PMB) remains a last-line treatment for MDR Gram-negative infections; however, its clinical use is restricted by nephrotoxicity, neurotoxicity, and the growing prevalence of resistance. This study reports the development of PMB-loaded silver nanoparticles (AgNPs) stabilized with polyvinylpyrrolidone (PVP) as a novel antimicrobial delivery system. The nanoparticles were synthesized via chemical reduction and optimized for PMB loading. The prepared nanoparticles were characterized using UV-vis spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). The optimized formulation (PMB-AgNPs-0.5) exhibited an average size of 95.9 ± 0.28 nm, a polydispersity index of 0.202 ± 0.06, encapsulation efficiency of 70.79 ± 2.5%, and a zeta potential of +2.82 mV. In antibacterial assays, PMB-AgNPs-0.5 significantly enhanced inhibition zones compared with free PMB and blank AgNPs: S. aureus (8.1 → 14.5 mm), E. coli (12.8 → 17.1 mm), and P. aeruginosa (12.9 → 17.2 mm). Notably, PMB-resistant S. aureus strains became sensitive, while PMB-sensitive E. coli and P. aeruginosa exhibited further increased susceptibility. Cytocompatibility studies in human dermal fibroblasts confirmed improved safety, with >80% cell viability maintained at bactericidal concentrations, compared with ∼75% for free PMB. These findings highlight PMB-loaded PVP-AgNPs as a promising nanotherapeutic platform with enhanced antibacterial efficacy, reduced toxicity, and significant potential as an effective strategy for combating multidrug-resistant (MDR) bacterial infections.
Insights
This study developed novel silver nanoparticles loaded with Polymyxin B (PMB) to combat multidrug-resistant bacteria. The PMB-loaded nanoparticles show enhanced antibacterial activity and reduced toxicity, offering a promising new treatment strategy.
Area of Science:
- Nanotechnology
- Microbiology
- Pharmacology
Background:
- Multidrug-resistant (MDR) bacteria present a critical global health challenge, diminishing antibiotic effectiveness.
- Polymyxin B (PMB) is a last-resort antibiotic for MDR Gram-negative infections but faces limitations due to toxicity and emerging resistance.
Purpose of the Study:
- To develop and characterize Polymyxin B-loaded silver nanoparticles (AgNPs) stabilized with polyvinylpyrrolidone (PVP) as an advanced antimicrobial delivery system.
- To evaluate the enhanced antibacterial efficacy and reduced toxicity of the novel nanotherapeutic formulation against MDR bacteria.
Main Methods:
- Silver nanoparticles (AgNPs) were synthesized via chemical reduction and loaded with PMB, stabilized by PVP.
- Nanoparticle characterization involved UV-vis spectroscopy, DLS, FTIR, TEM, and TGA.
- Antibacterial activity and cytocompatibility were assessed using bacterial inhibition assays and human dermal fibroblast studies.
Main Results:
- The optimized PMB-loaded AgNPs (PMB-AgNPs-0.5) measured approximately 95.9 nm with good encapsulation efficiency (70.79%).
- PMB-AgNPs-0.5 demonstrated significantly enhanced antibacterial activity against S. aureus, E. coli, and P. aeruginosa compared to free PMB.
- The formulation restored sensitivity in PMB-resistant strains and improved susceptibility in sensitive strains, while showing improved safety in human dermal fibroblasts.
Conclusions:
- PMB-loaded PVP-AgNPs represent a promising nanotherapeutic platform with superior antibacterial efficacy and reduced toxicity.
- This novel formulation offers a potential strategy for overcoming challenges posed by multidrug-resistant bacterial infections.
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