Metallic nanoparticles, such as gold nanoparticles (AuNPs), have been extensively studied as drug delivery systems for various therapeutic applications. However, drug-loaded-AuNPs have been rarely explored in vivo for their effect on bacteria residing inside tissues. Ciprofloxacin (CIP) is a second-generation fluoroquinolone with a broad-spectrum of antibiotic properties devoid of developing bacteria resistance. This research is focused on the synthesis and physical characterization of Ciprofloxacin-loaded gold nanoparticles (CIP-AuNPs) and their effect on the colonization of Enterococcus faecalis in the liver and kidneys of mice. The successfully prepared CIP-AuNPs were stable and exerted enhanced in vitro antibacterial activity against E. faecalis compared with free CIP. The optimized CIP-AuNPs were administered (500 µg/Kg) once a day via tail vein to infected mice for eight days and were found to be effective in eradicating E. faecalis from the host tissues. Moreover, unlike CIP, CIP-AuNPs were non-hemolytic. In summary, this study demonstrated that CIP-AuNPs are promising and biocompatible alternative therapeutics for E.-faecalis-induced infections resistant to conventional drugs (e.g., beta-lactams and vancomycin) and should be further investigated.

Pseudomonas aeruginosa is a Gram-negative pathogenic bacterium that is present commonly in soil and water and is responsible for causing septic shock, pneumonia, urinary tract and gastrointestinal infections, etc. The multi-drug resistance (MDR) phenomenon has increased dramatically in past years and is now considered a major threat globally, so there is an urgent need to develop new strategies to overcome drug resistance by P. aeruginosa. In P. aeruginosa, a major factor of drug resistance is associated to the formation of biofilms by the LasR enzyme, which regulates quorum sensing and has been reported as a new therapeutic target for designing novel antibacterial molecules. In this study, virtual screening and molecular docking were performed against the ligand binding domain (LBD) of LasR by employing a pharmacophore hypothesis for the screening of 2373 FDA-approved compounds to filter top-scoring hit compounds. Six inhibitors out of 2373 compounds were found to have binding affinities close to that of known LasR inhibitors. The binding modes of these compounds to the binding site in LasR-LBD were analyzed to identify the key interactions that contribute to the inhibition of LasR activity. Then, 50 ns simulations of top hit compounds were performed to elucidate the stability of their binding conformations with the LasR-LBD. This study, thus concluded that sulfamerazine showed the highest binding affinity for the LasR-LBD binding pocket exhibiting strong inhibitory binding interactions during molecular dynamics (MD) simulation.

Multidrug resistance (MDR) has been a potentiator for the exploration of antibiotics. Nano drug delivery systems have opened new avenues to overcome this challenge. Although antibacterial nanocarriers are extensively realized, their effect on the bacteria residing inside the tissues and their toxicity is rarely explored. This study investigated the effects of flavonoid coated gold nanoparticles (FAuNPs) on the colonization of Enterococcus faecalis in the mouse liver and kidneys. Flavonoids were extracted from the leaves of Berberis lycium Royle and used to stabilize gold following a green synthesis approach. FAuNPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning transmission electron microscopy (STEM), X-ray powder diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS). FAuNPs showed significantly higher reduction in bacterial counts in in-vitro and in-vivo in mice organs as compared to the free flavonoids owing to their biocompatibility and effectiveness.

Wilson’s disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a “thin film hydration method” was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats’ spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.

Leukaemia is a haematopoietic system malignancy depicted by the infiltration of the bone marrow, blood and other tissues by proliferative and abnormally differentiated cells of the haematopoietic system. The available therapies aim to induce cell death of these poorly differentiated cells by various means. The anthracycline doxorubicin (DOX) regime remains the standard first-line treatment for leukaemia. DOX has potent anticancer activity at higher dosage concentration and imparts cardiac, renal and hepatic toxicity. The disulfiram metabolite complex zinc diethyldithiocarbamate (Zn-DDC) has potent anticancer efficacy; however, it has a short half-life due to its instability in gastric juice and the blood stream. The present study employed a thin-film hydration method to synthesise liposomal nanoparticles encapsulating DOX (DOX-NPs), Zn-DDC (Zn-DDC-NPs) and both Zn-DDC and DOX (Zn-DDC + DOX-NPs). In vitro cytotoxicity and antioxidant assays were performed to assess their cytotoxicity and antioxidant activity. The liposomes were evaluated against leukaemia in Wistar rats. After leukaemia induction through benzene, haematological and serological assays, morphological and histological examinations were conducted to evaluate treatment approaches. All liposomal formulations overcame their limitations, improved the blood parameters (p > 0.05), restored the hepatic and renal enzyme levels (p > 0.05), and reduced the blast cells in blood and tissues. However, in co-encapsulated liposomes, Zn-DDC reduced the cytotoxicity caused by DOX and provided results more analogous to normal.