PEGylated niosomes co-loaded with nisin and ZnO nanoparticles enhance antibacterial and anti-biofilm activity against VRSA and P. aeruginosa
Background
Multidrug-resistant pathogens like vancomycin-resistant Staphylococcus aureus (VRSA) and ceftazidime-resistant Pseudomonas aeruginosa pose critical healthcare challenges due to their ability to form persistent biofilms and resist conventional antibiotics. Current treatments often struggle with limited efficacy, systemic toxicity, and poor penetration into biofilm matrices. This necessitates novel strategies for targeted drug delivery and enhanced antimicrobial action. Niosomes, as vesicular drug carriers, offer improved stability and controlled release, while PEGylation further enhances biocompatibility and circulation time, addressing key limitations in combating antimicrobial resistance (AMR) and biofilm-associated infections.
Study Design
Researchers developed PEGylated niosomes co-loaded with nisin (Nis) and biosynthesized zinc oxide nanoparticles (ZnO) (Nio-Nis/ZnO@PEG) using thin-film hydration followed by PEGylation. The formulation was characterized for size, morphology, and stability via DLS, TEM, SEM, and FTIR. Antibacterial activity was assessed by determining MIC/MBC values and inhibition zones. Anti-biofilm effects were evaluated through biomass reduction and MBEC against clinical and reference strains. Gene expression changes related to biofilm formation were quantified using qRT-PCR, and mammalian cell cytotoxicity was determined via MTT assay.
Results
The Nio-Nis/ZnO@PEG formulation demonstrated high encapsulation efficiency, sustained-release kinetics, and good physicochemical stability. It exhibited significantly lower MIC/MBC values and larger inhibition zones compared to free agents or non-PEGylated niosomes, with sustained bactericidal activity against both VRSA and ceftazidime-resistant P. aeruginosa (P < 0.001). Anti-biofilm assays revealed substantial efficacy:
The PEGylated formulation achieved > 80% biomass reduction and the lowest
MBECvalues across clinical and reference strains.qRT-PCRanalysis showed marked downregulation of all target biofilm-associated and quorum-sensing genes. Furthermore, cytotoxicity assays using theMTTmethod confirmed minimal adverse effects on mammalian cells, indicating good biocompatibility.
Key Findings
- PEGylated niosomes co-loaded with nisin and ZnO nanoparticles showed significantly lower
MIC/MBCvalues (P < 0.001) against VRSA and P. aeruginosa. - The formulation achieved > 80% biofilm biomass reduction and the lowest
MBECvalues against resistant strains. - Target biofilm-associated and quorum-sensing genes were markedly downregulated by the PEGylated niosomes.
- The Nio-Nis/ZnO@PEG formulation demonstrated high encapsulation efficiency, sustained release, and good stability.
- Minimal cytotoxicity was observed on mammalian cells, indicating good biocompatibility.
Why It Matters
This study introduces a highly promising strategy for combating multidrug-resistant bacterial infections and disrupting biofilms, which are notoriously difficult to treat. The co-delivery of nisin and ZnO nanoparticles within PEGylated niosomes offers a potent, broad-spectrum, and biocompatible approach. For peptide users and biohackers, this highlights the potential of advanced delivery systems to enhance the efficacy and safety of antimicrobial peptides like nisin. This formulation could lead to more effective protocols for topical or localized treatment of resistant infections, potentially reducing systemic antibiotic reliance. While currently an in vitro study, its strong performance supports further in vivo evaluation, moving closer to a clinically translatable protocol for challenging bacterial threats.
nisin
zinc-oxide
niosomes
pegylation
antibacterial
anti-biofilm