Antibiotic and inorganic nanoparticles co-loaded into carboxymethyl chitosan-functionalized niosome: Synergistic enhanced antibacterial and anti-biofilm activities

Niosomes are biocompatible nanocarriers that could be used for designing drug delivery systems. In this work, we report the synthesis, characterization and antibacterial/antibiofilm activity of a nanocomposite based on Sultamicillin tosylate (ST) and inorganic nanoparticles (i.e., zinc oxide or silver nanoparticles (ZnONPs/AgNPs)) co-loaded into niosome. Various formulations of this nanocomposite were prepared, and further coated with carboxymethyl chitosan (CMC) to enhance the antimicrobial and anti-biofilm activities. The optimized niosome had a particle size of 139.60 +/- 3.41 nm, PDI of 0.229 +/- 0.013, the zeta potential of -30.5 mV, encapsulation efficiency of 73.45 +/- 1.21%, and in vitro drug release of 65.84 +/- 1.22% at 48 h. The great stability of the prepared nanocomposite up to 30 days indicates its ability for future pharmaceutical applications. The synergistic effect between the Sultamicillin tosylate and inorganic nanoparticles on antibacterial and anti-biofilm properties of nanocomposite was determined against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae). The results of real-time PCR showed that ST-Nio-inorganic NPs@CMC down-regulated the icaA, MrkA, FimH, and arr biofilm-related gene expression with P <= 0.001. Additionally, MTT assay was performed to evaluate the cytotoxicity of the designed nanocomposite on human foreskin fibroblasts (HFF) cell line. The results indicated cell viability over 90% at all tested concentrations on HFF cells. Overall, the present study shows that the synergistic effects of ST and inorganic NPs loaded on niosome incorporated with CMC hydrogel is a useful strategy to enhance the antibacterial and antibiofilm activity of drugs and has high potential for biomedical application.