Vancomycin-gingerol encapsulated niosomal formulation against carbapenem-resistantKlebsiella pneumoniae.

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-resistantKlebsiella 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 thefimH, blaKPC, mrkD, andOmpk36genes 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.

In silico and in vitro studies of GENT-EDTA encapsulated niosomes: A novel approach to enhance the antibacterial activity and biofilm inhibition in drug-resistant Klebsiella pneumoniae.

Klebsiella pneumoniae (Kp) is a common pathogen inducing catheter-related biofilm infections. Developing effective therapy to overcome antimicrobial resistance (AMR) in Kp is a severe therapeutic challenge that must be solved. This study aimed to prepare niosome-encapsulated GENT (Gentamicin) and EDTA (Ethylenediaminetetraacetic acid) (GENT-EDTA/Nio) to evaluate its efficacy toward Kp strains. The thin-film hydration method was used to prepare various formulations of GENT-EDTA/Nio. Formulations were characterized for their physicochemical characteristics. GENT-EDTA/Nio properties were used for optimization with Design-Expert Software. Molecular docking was utilized to determine the antibacterial activity of GENT. The niosomes displayed a controlled drug release and storage stability of at least 60 days at 4 and 25 °C. GENT-EDTA/Nio performance as antimicrobial agents has been evaluated by employing agar well diffusion method, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) against the Kp bacteria strains. Biofilm formation was investigated after GENT-EDTA/Nio administration through different detection methods, which showed that this formulation reduces biofilm formation. The effect of GENT-EDTA/Nio on the expression of biofilm-related genes (mrkA, ompA, and vzm) was estimated using QRT-PCR. MTT assay was used to evaluate the toxicity effect of niosomal formulations on HFF cells. The present study results indicate that GENT-EDTA/Nio decreases Kp's resistance to antibiotics and increases its antibiotic and anti-biofilm activity and could be helpful as a new approach for drug delivery.