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Zinc oxide nanoparticles conjugated with clinically-approved medicines as potential antibacterial molecules.

ABSTRACT: At present, antibiotic resistance is one of the most pressing issues in healthcare globally. The development of new medicine for clinical applications is significantly less than the emergence of multiple drug-resistant bacteria, thus modification of existing medicines is a useful avenue. Among several approaches, nanomedicine is considered of potential therapeutic value. Herein, we have synthesized Zinc oxide nanoparticles (ZnO-NPs) conjugated with clinically-approved drugs (Quercetin, Ceftriaxone, Ampicillin, Naringin and Amphotericin B) with the aim to evaluate their antibacterial activity against several Gram-positive (Methicillin resistant Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes) and Gram-negative (Escherichia coli K1, Serratia marcescens and Pseudomonas aeruginosa) bacteria. The nanoparticles and their drug conjugates were characterized using UV-visible spectrophotometry, dynamic light scattering, Fourier transform infrared spectroscopy and atomic force microscopy. Antibacterial activity was performed by dilution colony forming unit method and finally 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine their cytotoxic effects against human cell lines. ZnO-NPs revealed maxima surface plasmon resonance band at 374 and after conjugation with beta-cyclodextrin at 379 nm, polydispersity with size in range of 25-45 nm with pointed shaped morphology. When conjugated with ZnO-NPs, drug efficacy against MDR bacteria was enhanced significantly. In particular, Ceftriaxone- and Ampicillin-conjugated ZnO-NPs exhibited potent antibacterial effects. Conversely, ZnO-NPs and drugs conjugated NPs showed negligible cytotoxicity against human cell lines except Amphotericin B (57% host cell death) and Amphotericin B-conjugated with ZnO-NPs (37% host cell death). In conclusion, the results revealed that drugs loaded on ZnO-NPs offer a promising approach to combat increasingly resistant bacterial infections.

SUBMITTER: Akbar N

PROVIDER: S-EPMC8272778 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:One major problem with the overuse of antibiotics is that the microorganisms acquire resistance; thus the dose must be increased unsustainably. To overcome this problem, researchers from around the world are actively investigating new types of antimicrobials. Zinc oxide (ZnO) nanoparticles (NPs) have been proven to exhibit strong antimicrobial effects; moreover, the Food and Drugs Administration (FDA) considers ZnO as GRAS (generally recognized as safe). Many essential oils have antimicrobial activity and their components do not generate resistance over time. One of the drawbacks is the high volatility of some components, which diminishes the antimicrobial action as they are eliminated. The combination of ZnO NPs and essential oils can synergistically produce a stronger antimicrobial effect, and some of the volatile compounds can be retained on the nanoparticles' surface, ensuring a better-lasting antimicrobial effect. The samples were characterized with X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), and thermal analysis (TG-DSC) coupled with analysis of evolved gases using FTIR. The ZnO NPs, with a size of ~35 nm, exhibited a loading between 1.44% and 15.62%-the lower values were specific for limonene-containing oils (e.g., orange, grapefruit, bergamot, or limette), while high values were obtained from cinnamon, minzol, thyme, citronella, and lavender oils-highlighting differences among non-polar terpenes and alcohol or aldehyde derivatives. The antibacterial assay indicated the existence of a synergic action among components and a high dependency on the percentage of loaded oil. Loaded nanoparticles offer immense potential for the development of materials with specific applications, such as wound dressings or food packaging. These nanoparticles can be utilized in scenarios where burst delivery is desired or when prolonged antibacterial activity is sought.

Project description:BackgroundHerein, we first time used the gum Moringa oleifera as reducing and capping agent for successful synthesis of silver nitrate and zinc oxide nanoparticles(NPs) through green synthesis approach. This study was aimed to check antibacterial activities of synthesized NPs against multidrug resistant bacteria methicillin-resistant Staphylococcus aureus (MRSA).MethodsAqueous solutions of AgNO3 and purified gum powder were mixed with 1:1 ratio, autoclaved at 120oC for 2 min. NPs pellet collected after centrifugation at 10,000 g for 20 min. ZnO NPs were prepared by mixing purified gum powder and metal salt with1:1 ratio, heated (70oC) and stirred at 100 rpm for 4 h followed by centrifugation at 10,000 g for 20 min. Pellet was washed and calcinated at 400oC for 4 h. Antibacterial potential against E. coli, S. aureus and methicillin-resistant Staphylococcus aureus (MRSA) was assessed by widely used Kirby-Bauer antibiotic susceptibility test.ResultsOptical observation of colour change from transparent to dark and UV-Visible analysis confirmed the synthesis of NPs. Fourier transform infrared spectroscopy (FTIR) of prepared nonmaterial revealed the characteristic AgNPs and ZnO stretch vibrations at wave number of 523 cm- 1 and 471 cm- 1resectively. Crystalline nature of AgNPs and ZnO NPs was confirmed by x-ray diffraction pattern with clear sharp Peaks. Scanning electron microscopy (SEM) revealed good surface morphology of AgNPs and ZnO NPs with 50nm and 60nm size respectively. AgNPs and ZnO NPs exhibited excellent antibacterial activity against E. coli (with zone of inhibition of 21 ± 02mm and 22 ± 03mm) and S.aureus ( with zone of inhibition of 20 ± 03mm and 21 ± 02mm) while good activity was observed against "super bug" methicillin-resistant Staphylococcus aureus (MRSA) with 16 ± 03mm ad 17 ± 02mm zone if inhibitions respectively.ConclusionsThis novel addition of Moringa Gum based nanoparticles will open new dimensions in the field of nanomedicine and pharmaceutics especially against MDR bacterial strains.

Project description:BACKGROUND:Novel methods are necessary to reduce morbidity and mortality of patients suffering from infections with Pseudomonas aeruginosa. Being the most common infectious species of the Pseudomonas genus, P. aeruginosa is the primary Gram-negative etiology responsible for nosocomial infections. Due to the ubiquity and high adaptability of this species, an effective universal treatment method for P. aeruginosa infection still eludes investigators, despite the extensive research in this area. RESULTS:We report bacterial inhibition by iron-oxide (nominally magnetite) nanoparticles (NPs) alone, having a mean hydrodynamic diameter of?~?16 nm, as well as alginate-capped iron-oxide NPs. Alginate capping increased the average hydrodynamic diameter to?~?230 nm. We also investigated alginate-capped iron-oxide NP-drug conjugates, with a practically unchanged hydrodynamic diameter of?~?232 nm. Susceptibility and minimum inhibitory concentration (MIC) of the NPs, NP-tobramycin conjugates, and tobramycin alone were determined in the PAO1 bacterial colonies. Investigations into susceptibility using the disk diffusion method were done after 3 days of biofilm growth and after 60 days of growth. MIC of all compounds of interest was determined after 60-days of growth, to ensure thorough establishment of biofilm colonies. CONCLUSIONS:Positive inhibition is reported for uncapped and alginate-capped iron-oxide NPs, and the corresponding MICs are presented. We report zero susceptibility to iron-oxide NPs capped with polyethylene glycol, suggesting that the capping agent plays a major role in enabling bactericidal ability in of the nanocomposite. Our findings suggest that the alginate-coated nanocomposites investigated in this study have the potential to overcome the bacterial biofilm barrier. Magnetic field application increases the action, likely via enhanced diffusion of the iron-oxide NPs and NP-drug conjugates through mucin and alginate barriers, which are characteristic of cystic-fibrosis respiratory infections. We demonstrate that iron-oxide NPs coated with alginate, as well as alginate-coated magnetite-tobramycin conjugates inhibit P. aeruginosa growth and biofilm formation in established colonies. We have also determined that susceptibility to tobramycin decreases for longer culture times. However, susceptibility to the iron-oxide NP compounds did not demonstrate any comparable decrease with increasing culture time. These findings imply that iron-oxide NPs are promising lower-cost alternatives to silver NPs in antibacterial coatings, solutions, and drugs, as well as other applications in which microbial abolition or infestation prevention is sought.

Project description:Owing to the peculiar broad-spectrum antimicrobial activities of zinc oxide nanoparticles (ZnO NPs), we envisaged their use to treat bacterial/mycobacterial/fungal infections during peritoneal dialysis (PD) of end-stage renal failure patients. However, a recent study from our lab showed that ZnO-NPs cannot be employed for the same in their naked form owing to their rapid agglomeration. Also, the naked ZnO-NPs showed strong interaction with organic acids present in the PD fluid (i.e., lactate and citrate present abundantly in almost all biological fluids) resulting in the formation of bioconjugates. Here, we propose that the surface coating of ZnO NPs may inhibit the binding interactions of NPs with the constituents of PD fluid. Therefore, in this study, we have carried out the surface coating of ZnO NPs with polyethylene glycol (PEG) of different molecular weights, followed by the investigations of physicochemical properties of PEGylated ZnO NPs dispersed in PD fluid using nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. The interaction of PEGylated ZnO NPs has also been studied separately in glucose and lactic acid which are the main constituents of PD fluid and in citric acid. Although the X-ray diffraction and TEM results infer the colloidal stability of PEGylated ZnO NPs in PD fluid, FT-IR, UV-vis, and nuclear magnetic resonance results revealed the binding interactions of PEGylated ZnO NPs with the PD constituents. PEGylated ZnO NPs also interact strongly with the lactic acid and citric acid, leading to agglomeration, as observed previously for uncoated ZnO NPs. Further, the antibacterial activities of bare and PEG-coated ZnO NPs dispersion in PD fluid have been studied. A reduction in the bacterial inhibition effect against Staphylococcus aureus and Escherichia coli was observed for both the bare and PEG-coated ZnO NPs dispersed in PD fluid, indicating that the complex nature of PD fluid counteract on the efficiency of these nanobiotics.

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Zinc oxide nanoparticles conjugated with clinically-approved medicines as potential antibacterial molecules.

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