Abstract

Alternatives to conventional antibiotics are critical in light of the increasing prevalence of antibiotic-resistant bacteria, posing a serious threat to humanity and imposing a financial burden on the community. The current study aimed to develop a Vancomycin (Van) and Gingerol (Gin) co-encapsulated in a niosomal (Nio-Gin/Van) formulation and to assess the optimized formulation as a potent antibacterial agent against carbapenem-resistant Klebsiella pneumoniae (CRKP) strains. The prepared Nio-Gin/Van was characterized via scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) and Fourier-transform infrared spectroscopy (FTIR) techniques. The F4 formulation was selected as the optimal formulation due to its low polydispersity index (PDI) (0.221 ± 0.023), small size (222.8 ± 6.35 nm), and suitable entrapment efficiency (EE%) (83.73 ± 1.12 for Gin and 66.25 ± 1.34 for Van). The Nio-Gin/Van had a sustained drug release up to 72 h and posed great stability to 60 d at 4 °C with low alterations in size, PDI and EE%, which introduced it as an appropriate candidate for medicinal utilization. The antibacterial activities of Nio-Gin/Van against CRKPs isolates were investigated using a MIC assay, which revealed MIC values of between 7.81/100–125/100 μg ml−1. Microtiter-plate assays and real-time polymerase chain reaction (PCR) were used to evaluate the antibiofilm properties of Nio-Gin/Van. A microtiter-plate assay indicated that approximately 53% of 15 CRKP isolates (n = 8) produced strong biofilms, while 26.6% (n = 4) produced moderate biofilms. Additionally, real-time PCR analysis revealed that Nio-Gin/Van significantly reduced the expression of the fimH, blaKPC, mrkD, and Ompk36 genes in all CRKP isolates examined. It was concluded that encapsulating Gin-Van in niosome enhances their antibacterial and antibiofilm activity against CRKP strains and these preparations could be considered as a novel strategy for targeted drug delivery.

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