Solid lipid nanoparticle formulation maximizes membrane-damaging efficiency of antimicrobial nisin Z peptide

Solid lipid nanoparticles (SLNs) can protect and deliver naturally derived or synthetic biologically active products to target sites in vivo. Here, an SLN formulation produces a measured four-fold reduction in inhibitory concentration of an antimicrobial peptide nisin Z against S. aureus as compared to the free peptide, indicating the successful delivery and enhanced effectiveness of the SLN-encapsulated bacteriocin. Spherical SLNs of size 79.47 ± 2.01 nm and zeta potential of −9.8 ± 0.3 mV were synthesised. The lipid formulation maximizes the membrane-damaging mode of action of the free peptide with more and larger-sized pores formed on bacterial membranes treated with nisin Z SLNs as measured from scanning electron microscopy and transmission electron microscopy. Flow cytometry measurements precisely quantified an enhanced dye leakage from pre-labeled bacterial cells when treated with nisin Z-loaded SLNs compared to free peptide. The lipid formulation accelerated cell death by killing all the cells within half an hour compared to the equivalent concentration of free peptide which was not bactericidal. Molecular dynamics simulations revealed a mechanism of SLN facilitated binding to the lipid II bacterial cell wall precursor via enhanced adsorption of nisin Z at the inner bacterial cell membrane bilayer. These findings confirmed the potential of SLN formulations for the effective delivery of therapeutic peptides for next-generation antibiotics that are active at low concentrations with the potential to mitigate antimicrobial resistance.