Synergistic effect of curcumin-Cu and curcumin-Ag nanoparticle loaded niosome: Enhanced antibacterial and anti-biofilm activities.

In the current study, for the first time, the synergistic activity of curcumin and silver/copper nanoparticles (NPs) was studied against Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, a unique combination of curcumin and silver/copper NPs in free and encapsulated forms was prepared and delivered through a niosomal system. For this purpose, different niosomal formulations of curcumin and metal NPs were prepared by thin film hydration method. Then, the dual drug-loaded niosomes were dispersed in chitosan hydrogel in order to widen its applications. The effect of the molar ratios of lipid to drug and surfactant to cholesterol was investigated to find the optimized noisomal nanoparticles in terms of size, polydispersity index (PDI), and entrapment efficiency (EE). The size and PDI values were measured by dynamic light scattering (DLS). Morphology and in vitro drug release kinetics of niosomes were examined by scanning and transmission electron microscopy (SEM, TEM) and dialysis method, respectively. The drug-loaded niosomes and their hydrogel counterpart were screened for investigating their antibacterial activity against S. aureus and P. aeruginosa by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Furthermore, anti-biofilm assay and expression of biofilm-associated genes by Real-time PCR were performed to evaluate the anti-biofilm effect of NPs. In this study, the drug-loaded niosomal formulations showed good entrapment efficiencies (EE) with a sustained release profile over 72 h. Moreover, compared to free drugs, the optimized niosomal formulations increased antibacterial activity against the bacteria via promotion in the inhibition zone and reduction in MIC and MBC values. Interestingly, gel-based niosomal formulations increased the inhibition zone by about 6 mm and significantly decreased MIC and MBC values compared to niosomal formulations. Also, biofilm eradication of curcumin-metal NPs encapsulated into niosomal hydrogel was highest compared to free and niosomal drugs. Overall, curcumin-Cu or curcumin-Ag nanoparticle loaded niosomes incorporated in hydrogel hold great promise for biomedical applications.