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In the last few decades, pharmaceuticals have emerged as a new class of serious environmental pollutants. The presence of these emerging contaminants even in minimal amounts (micro- to nanograms) has side effects, and they can cause chronic toxicity to health and the environment. Furthermore, the presence of pharmaceutical contaminants in water resources leads to significant antibiotic resistance in bacteria. Hence, the removal of antibiotics from water resources is essential. Thus far, a wide range of methods, including adsorption, photodegradation, oxidation, photolysis, micro-/nanofiltration, and reverse osmosis, has been used to remove pharmaceutical contaminants from water systems. In this article, research related to the processes for the removal of metronidazole antibiotics from water and wastewater, including adsorption (carbon nanotubes (CNTs), magnetic nanocomposites, magnetic molecularly imprinted polymer (MMIP), and metal-organic frameworks), filtration, advanced oxidation processes (photocatalytic process, electrochemical advanced oxidation processes, sonolysis and sonocatalysis) and aqueous two-phase systems (ATPSs), was reviewed. Results reveal that advanced oxidation processes, especially photocatalytic and sonolysis processes, have high potential in removing MNZ (more than 90%).

To enhance the effects of some functional soft drinks, drugs, especially metronidazole (MNZ) and ibuprofen (IBF), are often illegally added. This poses a serious threat to the health of consumers. Therefore, developing simple and rapid detection methods for these additives is crucial. In this study, DNA aptamers of metronidazole and ibuprofen were selected using the library-immobilized method. The best aptamer for metronidazole, named MNZ-1, has a dissociation constant ( K d ) value of 4.9 μM and the aptamer for ibuprofen, named IBF-1, shows a K d of 9.3 μM, as determined by the thioflavin T (ThT) fluorescence assay. The K d values measured using isothermal titration calorimetry (ITC) were 17.0 μM and 66.7 μM for these two aptamers, respectively. Selectivity experiments indicate that MNZ-1 demonstrates very weak binding to structurally similar drugs, whereas IBF-1 exhibits binding capability to some structurally similar compounds comparable to ibuprofen, enabling the simultaneous detection of these types of drugs. Neither MNZ-1 nor IBF-1 binds to other common drugs. Using ThT, a label-free fluorescent detection method was developed for metronidazole and ibuprofen in soft drinks, showing limits of detection (LODs) of 0.6 μM and 4.7 μM, respectively. Owing to their small size and well-defined secondary structures, these aptamers are expected to be utilized in analytical applications for food and environmental monitoring.

The hypoxic microenvironment of solid tumors can lead to reduced therapeutic DNA damage to the tumor cells, thus diminishing tumor sensitivity to radiotherapy. Although hypoxic radiosensitizers can improve radiotherapy efficacy by enhancing the role of oxygen, their effects are limited by the uneven distribution of oxygen within solid tumor tissues. In this study, a novel radiosensitizer via leveraging gold complexes and metronidazole (MN) was synthesized to improve radiotherapeutic efficacy. The gold atoms incorporated in the radiosensitizer enabled efficient deposition of high-energy radiation; the hydrophobic metronidazole was reduced to hydrophilic aminoimidazole under hypoxia conditions and further promoted radiotherapy sensitization. The results of CCK-8 assays, Live/Dead assays, γ-H 2 AX immunofluorescence indicated that metronidazole-modified Au@BSA nanocomposites (NCs) exhibited excellent antitumor effects. The in vivo antitumor tests further showed an inhibition rate of 100%. These results demonstrated that the NCs successfully enhanced radiotherapy efficacy by the dual sensitization strategy. Overall, we believe this multimodal radiosensitizing nanocomplex can significantly inhibit tumor growth and metastasis, with their hypoxia-oriented characteristics ensuring a higher efficacy and safety.

Background: Currently, many natural gums are extensively utilized as suspending agents in the formulation of pharmaceutical suspensions. They are easily available, nontoxic, biodegradable, and cost-effective to be used as pharmaceutical excipients. Objective: The present study was aimed at physicochemical characterization and evaluation of the suspending capacity of Boswellia papyrifera gum (BPG) in comparison with sodium carboxy methyl cellulose (SCMC) and tragacanth gum (TG). Methods: The extracted and powdered BPG was subjected to physicochemical properties such as micromeritics, solubility, swelling power, ash value, moisture content, conductivity, pH, and apparent viscosity using standard methods. Metronidazole benzoate suspensions were formulated using various concentrations of BPG, SCMC, and TG (1%-5% w / v ). The apparent viscosity, flow rate, sedimentation volume, redispersibility number, pH, and drug content were studied as assessment parameters. Results: The micromeritic studies revealed that BPG exhibited good flow properties. There was also a significant increase in solubility and swelling power of the gum as a function of temperature. The gum had 2.78% ash value and 4.32% moisture content. Conductivity and apparent viscosity of the gum were found to be increased with concentration ( p < 0.05). However, the apparent viscosity of BPG was decreased with shear rate ( p < 0.05), rendering a pseudoplastic flow property of the gum, which is an ideal characteristic of suspending agents. The suspending capacity of the BPG was found to be comparable to SCMC, but higher than TG. Thus, it can be concluded that BPG could be used as the best alternative to natural and synthetic suspending agents., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Gebremariam Woldu et al.)

Since its application in environmental remediation, nano zero-valent iron (nZVI) has gained wide attention for its environmental friendliness, strong reducing ability, and wide range of raw materials. However, its high preparation cost and difficulty in preservation remain the bottlenecks for their application. Carbothermal reduction is a promising method for the industrial preparation of nZVI. Micronized zero-valent iron/carbon materials (Fe 0 /CB) were produced in one step by co-pyrolysis of carbon and iron. The performance of the Fe 0 /CB is comparable to that of nZVI. In addition, Fe 0 /CB overcomed the disadvantages of agglomeration and oxidative deactivation of nZVI. Experiments on the Fenton-like reaction of its activated PDS showed that metronidazole (MNZ) was efficiently removed through the synergistic action of radicals and non-radicals, which were mainly superoxide radicals (·O 2 - ), monoclinic oxygen ( 1 O 2 ), and high-valent iron (Fe IV O). Moreover, the degradation process showed better generalization, making it suitable for a wide range of applications in the degradation of antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study aimed to advance the development of intestinal colon-coated sustained-release matrix tablets of metronidazole for diverticulitis treatment, employing the Quality by Design (QbD) methodology. Comprehensive Risk analysis and Risk evaluation were conducted to assess the potential risks associated with Critical Material Attributes (CMA) and Critical Process Parameters (CPP). Ishikawa diagram, color-coded risk classification and the Risk Priority Number (RPN) were used as tools for risk evaluation. A Design of Experiments (DoE) was executed using a fractional factorial design, incorporating five key factors derived from the Risk analysis and Risk evaluation. Two levels and a central point were established for each factor, resulting in 28 batches of coated tablets. The manufacturing process involved direct compression, followed by a coating process using pH-dependent or time-dependent polymers. Characterization and dissolution studies were conducted on all batches, and the obtained results underwent analysis of variance (ANOVA). The findings demonstrated the robustness and reproducibility of both the direct compression and coating processes. Statistical analysis identified HPMC/chitosan ratio, blending time, coating polymer, and coating weight gain as factors significantly impacting drug release. A Design Space was established to delineate the interplay of these factors, offering insights into various combinations influencing drug release behavior. Thus, the design space for 10 % weight gain formulations includes a range of HPMC/CH ratios between 2.7-3 and mixing times between 10 and 12 min; for 20 % weight gain formulations it includes a range of HPMC/CH ratios up to 2 and mixing times between 10 and 16 min. Multiple Linear Regression between technological and biopharmaceutical variables were optimized facilitating scale-up operations. Batches with a 10 % weight increase and varied HPMC viscosity grades and coating polymers achieve ∼50 % drug release at 24 h; however, batches with a 20 % weight increase along, with either high proportions of HPMC and short blending times or low proportions of HPMC and longer blending times, achieve slow release of metronidazole. This study contributes to optimizing metronidazole colonic delivery systems, enhancing their potential efficacy in diverticulitis treatment., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bacterial vaginosis (BV) is an imbalance of the vaginal microbiome in which there are limited lactobacilli and an overgrowth of anaerobic and fastidious bacteria such as Gardnerella. The propensity for BV recurrence is high, and therapies involving multiple treatment modalities are emerging to meet this need. However, current treatments requiring frequent therapeutic administration are challenging for patients and impact user compliance. Three-dimensional (3D)-printing offers a novel alternative to customize platforms to facilitate sustained therapeutic delivery to the vaginal tract. This study designed a novel vehicle intended for dual sustained delivery of both antibiotic and probiotic. 3D-printed compartmental scaffolds consisting of an antibiotic-containing silicone shell and a core containing probiotic Lactobacillus were developed with multiple formulations including biomaterials sodium alginate (SA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyethylene oxide (PEO), and kappa-carrageenan (KC). The vehicles were loaded with 50 μg of metronidazole/mg polymer and 5 × 10 7 CFU of L. crispatus/mg scaffold. Metronidazole-containing shells exhibited cumulative drug release of 324.2 ± 31.2 μg/mL after 14 days. Multiple polymeric formulations for the probiotic core demonstrated cumulative L. crispatus recovery of >5 × 10 7 CFU/mg scaffold during this timeframe. L. crispatus-loaded polymeric formulations exhibited ≥2 log CFU/mL reduction in free Gardnerella in the presence of VK2/E6E7 vaginal epithelial cells. As a first step towards the goal of facilitating patient compliance, this study demonstrates in vitro effect of a novel 3D-printed dual antibiotic and probiotic delivery platform to target BV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A facile and simple electrochemical composite sensor, CDs-Ag@Cu 2 O-GA, prepared from carbon dots stabilized silver nanoparticles and copper oxide, was used as an electrocatalyst and signal amplifier for the non-enzymatic detection of antibiotic traces in food products. The prepared composite demonstrated excellent stability, sensitivity, and cost-effectiveness. The sensor was constructed by modifying a glassy carbon electrode (GCE) with CDs-Ag@Cu 2 O-GA, and the electroanalytical response was determined for the precise determination of metronidazole (MTZ) drug traces in milk. The analytical response signified fast electron transfer and accessibility of several electroactive sites, producing an amplified response for the reduction of MTZ. The quantitative analysis by the sensor revealed a good linear range (10-110 μM), a low limit of detection (7.1 × 10 -7 molL -1 ), and a high sensitivity (1.5 μA μM -1  cm -2 ). Furthermore, the sensor displayed excellent potential for practical applications, verified by the good recovery of the drug from spiked milk samples., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mustansara yaqub reports financial support was provided by COMSATS University Islamabad - Lahore Campus. Mustansara Yaqub reports a relationship with COMSATS University Islamabad - Lahore Campus that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Antimicrobial resistance (AMR) has been emerging as a major global health threat and calls for the development of novel drug candidates. Metal complexes have been demonstrating high efficiency as antibacterial agents that differ substantially from the established types of antibiotics in their chemical structures and their mechanism of action. One strategy to exploit this potential is the design of metal-based hybrid organometallics that consist of an established antibiotic and a metal-based warhead that contributes an additional mechanism of action different from that of the parent antibiotic. In this communication, we describe the organometallic hybrid antibiotic 2c, in which the drug metronidazole is connected to a gold(I) N-heterocyclic carbene warhead that inhibits bacterial thioredoxin reductase (TrxR). Metronidazole can be used for the treatment with the obligatory anaerobic pathogen Clostridioides difficile (C. difficile), however, resistance to the drug hampers its clinical success. The gold organometallic conjugate 2c was an efficient inhibitor of TrxR and it was inactive or showed only minor effects against eucaryotic cells and bacteria grown under aerobic conditions. In contrast, a strong antibacterial effect was observed against both metronidazole-sensitive and -resistant strains of C. difficile. This report presents a proof-of-concept that the design of metal-based hybrid antibiotics can be a viable approach to efficiently tackle AMR., (© 2024. The Author(s).)

Periodontitis is a common chronic inflammatory disease primarily caused by the prevalence of bacterial overgrowth resulting in the development of an inflammatory condition that destroys the tooth's supporting tissues and eventual tooth loss. Comparatively, to other treatment methods, it is difficult for topical antibacterial drugs to effectively permeate the biofilm's physical barrier, making conventional therapy for periodontitis more challenging. This novel study combines thermosensitive in situ hydrogel with microparticles (MPs) to enhance the targeted delivery of metronidazole (MET) to the periodontal pocket. Polycaprolactone (PCL) polymer was utilized to produce bacteria-sensitive MPs. Additionally, the study assessed the attributes of MPs and demonstrated an enhancement in the in vitro antibacterial efficacy of MPs towards Staphylococcus aureus (SA) and Escherichia coli (EC). Subsequently, we incorporated MET-MPs into thermosensitive in situ hydrogel formulations using chitosan. The optimized formulations exhibited stability, appropriate gelation temperature, mucoadhesive strength, and viscosity. In vitro permeation tests showed selective and prolonged drug release against SA and EC. Ex vivo experiments demonstrated no significant differences between in situ hydrogel containing pure MET and MET-MPs in biofilm quantity, bacterial counts, and metabolic activity in biofilms. According to in vitro tests and the effectiveness of the antibacterial activity, this study has exhibited a novel methodology for more efficacious therapies for periodontitis. This study aims to utilize MET in MPs to improve its effectiveness, enhance its antibacterial activity, and improve patient treatment outcomes. In further research, the efficacy of the treatment should be investigated in vivo using an appropriate animal model.

The utilization of natural materials for the synthesis of highly fluorescent carbon quantum dots (CQDs) presents a sustainable approach to overcome the challenges associated with traditional chemical precursors. Here, we report the synthesis of novel S,N-self-doped CQDs (S,N@CQDs) derived from asparagus officinalis herb. These S,N@CQDs exhibit 16.7 % fluorescence quantum yield, demonstrating their potential in medical diagnostics. We demonstrate the efficacy of S,N@CQDs as luminescent probes for the detection of anti-pathogenic medications metronidazole (MTZ) and nitazoxanide (NTZ) over concentration ranges of 0.0-180.0 μM (with a limit of detection (LOD) of 0.064 μM) and 0.25-40.0 μM (LOD of 0.05 μM), respectively. The probes were successfully applied to determine MTZ and NTZ in medicinal samples, real samples, and spiked human plasma, with excellent recovery rates ranging from 99.82 % to 103.03 %. Additionally, S,N@CQDs demonstrate exceptional efficacy as diagnostic luminescent probes for hemoglobin (Hb) detection over a concentration range of 0-900 nM, with a minimal detectability of 9.24 nM, comparable to commercially available medical laboratory diagnostic tests. The eco-friendly synthesis and precise detection limits of S,N@CQDs meet necessary analytical requirements and hold promise for advancing diagnostic capabilities in clinical settings. This research signifies a significant step towards sustainable and efficient fluorescence-based medical diagnostics., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The presence of metronidazole (MNZ) and acetaminophen (ACE) in aquatic environments has raised growing concerns regarding their potential impact on human health. Incorporating various patterns into a photocatalytic material is considered a critical approach to achieving enhanced photocatalytic efficiency in the photocatalysis process. In this study, WO 3 nanoparticles, which were immobilized onto ferromagnetic multi-walled carbon nanotubes that were functionalized using (3-glycidyloxypropyl)trimethoxysilane (FMMWCNTs@GLYMO@WO 3 ), exhibited remarkable efficiency in removing MNZ and ACE (93% and 97%) in only 15 min. In addition, the new visible-light FMMWCNTs@GLYMO@WO 3 nanoparticles as a magnetically separable photocatalyst were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), EDS-mapping, vibrating sample magnetometry (VSM), thermogravimetric analysis (TGA), diffuse reflectance spectroscopy (DRS), high-performance liquid chromatography (HPLC), and total organic carbon (TOC) due to detailed studies (morphological, structural, magnetic and optical properties) of the photocatalyst. In-depth spectroscopic and microscopic characterization of the newly developed ferromagnetic FMMWCNTs@GLYMO@WO₃ (III) photocatalyst revealed a spherical morphology, with nanoparticle diameters averaging between 23 and 39 nm. Compared to conventional multiwall carbon nanotube and WO₃ photocatalysts, FMMWCNTs@GLYMO@WO₃ (III) demonstrated superior photocatalytic activity. Remarkably, it exhibited excellent reusability, maintaining its efficiency over a minimum of five cycles in the degradation of metronidazole (MNZ) and acetaminophen (ACE)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A unique approach is imperative for the development of drugs aimed at inhibiting various stages of infection, rather than solely focusing on bacterial viability. Among the array of unconventional targets explored for formulating novel antimicrobial medications, blocking the quorum-sensing (QS) system emerges as a highly effective and promising strategy against a variety of pathogenic microbes. In this investigation, we have successfully assessed nine α-aminoamides for their anti-QS activity using Agrobacterium tumefaciensNT1 as a biosensor strain. Among these compounds, three (2, 3and, 4) have been identified as potential anti-QS candidates. Molecular docking studies have further reinforced these findings, indicating that these compounds exhibit favorable pharmacokinetic profiles. Additionally, we have assessed the ligand's stability within the protein's binding pocket using molecular dynamics (MD) simulations and MMGBSA analysis. Further, combination of antiquorum sensing properties with antibiotics viaself-assembly represents a promising approach to enhance antibacterial efficacy, overcome resistance, and mitigate the virulence of bacterial pathogens. The release study also reflects a slow and gradual release of the metronidazole at both pH 6.5 and pH 7.4, avoiding the peaks and troughs associated with more immediate release formulations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Manoj K. Gupta has patent A Multicomponent Process for Peptoid Synthesis with Anti-Quorum Sensing Properties licensed to Vinod Kumar, Manoj K. Gupta, Central University of Haryana. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metronidazole (MNZ), a commonly used antibiotic, poses risks to water bodies and human health due to its potential carcinogenic, mutagenic, and genotoxic effects. In this study, mesoporous cobalt-manganese layered double hydroxides (Co x Mn y -LDH) with abundant oxygen vacancies (O v ) were successfully synthesized using the co-precipitation method and used to activate calcium sulfite (CaSO 3 ) with slight soluble in water for MNZ degradation. The characterization results revealed that Co 2 Mn-LDH had higher specific areas and exhibited good crystallinity. Co 2 Mn-LDH/CaSO 3 exhibited the best catalytic performance under optimal conditions, achieving a remarkable MNZ degradation efficiency of up to 98.1 % in only 8 min. Quenching experiments and electron paramagnetic resonance (EPR) tests showed that SO 4 •- and 1 O 2 played pivotal roles in the MNZ degradation process by activated CaSO 3 , while the redox cycles of Co 2+ /Co 3+ and Mn 3+ /Mn 4+ on the catalyst surface accelerated electron transfer, promoting radical generation. Three MNZ degradation routes were put forward based on the density functional theory (DFT) and liquid chromatography-mass spectrometer (LC-MS) analysis. Meanwhile, the toxicity analysis result demonstrated that the toxicity of intermediates post-catalytic reaction was decreased. Furthermore, the Co 2 Mn-LDH/CaSO 3 system displayed excellent stability, reusability, and anti-interference capability, and achieved a comparably high removal efficiency across various organic pollutant water bodies. This study provides valuable insights into the development and optimization of effective heterogeneous catalysts for treating antibiotic-contaminated wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Biocompatible and highly fluorescent phosphorus, nitrogen and sulfur carbon quantum dots (P,N,S-CQDs) were synthesized using a quick and ecologically friendly process inspired from plant sources. Garlic and red lentils were utilized as natural and inexpensive sources for efficient synthesis of the carbon-based quantum dots using green microwave-irradiation, which provides an ultrafast route for carbonization of the organic biomass and subsequent fabrication of P,N,S-CQDs within only 3 min. The formed P,N,S-CQDs showed excellent blue fluorescence at λ em  = 412 nm when excited at 325 nm with a quantum yield up to 26.4%. These fluorescent dots were used as a nano-sensor for the determination of the commonly used antibacterial and antiprotozoal drug, metronidazole (MTR). As MTR lacked native fluorescence and prior published techniques had several limitations, the proposed methodology became increasingly relevant. This approach affords sensitive detection with a wide linear range of 0.5-100.0 μM and LOD and LOQ values of 0.14 μM and 0.42 μM, respectively. As well as, it is cost-effective and ecologically benign. The MTT test was used to evaluate the in-vitro cytotoxicity of the fabricated P,N,S-CQDs. The findings supported a minimally cytotoxic impact and good biocompatibility, which provide a future perspective for the applicability of these CQDs in biomedical applications., (© 2024 John Wiley & Sons, Ltd.)

This study investigates the potential applications of incorporating 2D bacterial cellulose microfibers (BCM) biochar into chitosan/polyethyleneimine beads as a semi-natural sorbent for the efficient removal of tetracycline (TET) and metronidazole (MET) antibiotics. Batch adsorption experiments and characterization techniques evaluate removal performance and synthesized adsorbent properties. The adsorbent eliminated 99.13 % and 90 % of TET and MET at a 10 mg.L -1 concentration with optimal pH values of 8 and 6, respectively, for 90 min. Under optimum conditions and a 400 mg.L -1 concentration, MET and TET have possessed the maximum adsorption capacities of 691.325 and 960.778 mg.g -1 , respectively. According to the isothermal analysis, the adsorption of TET fundamentally follows the Temkin (R 2  = 0.997), Redlich-Peterson (R 2  = 0.996), and Langmuir (R 2  = 0.996) models. In contrast, the MET adsorption can be described by the Langmuir (R 2  = 0.997), and Toth (R 2  = 0.991) models. The pseudo-second-order (R 2  = 0.998, 0.992) and Avrami (R 2  = 0.999, 0.999) kinetic models were well-fitted with the kinetic results for MET and TET respectively. Diffusion models recommend that pore, liquid-film, and intraparticle diffusion govern the rate of the adsorption process. The developed semi-natural sorbent demonstrated exceptional adsorption capacity over eleven cycles due to its porous bead structure, making it a potential candidate for wastewater remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The traditional delivery of metronidazole and theophylline presents challenges like bitter taste, variable absorption, and side effects. However, gel-based systems offer advantages including enhanced targeted drug delivery, minimized side effects, and improved patient compliance, effectively addressing these challenges. Consequently, a cost-effective synthesis of N-hydroxyalkanamide gelators with varying alkyl chain lengths was achieved in a single-step reaction procedure. These gelators formed self-assembled aggregates in DMSO/water solvent system, resulting in organo/hydrogels at a minimum gelation concentration of 1.5 % w/v. Subsequently, metronidazole and theophylline were encapsulated within the gel core and released through gel-to-sol transition triggered by pH variation at 37 °C, while maintaining the structural-activity relationship. UV-vis spectroscopy was employed to observe the drug release behavior. Furthermore, in vitro cytotoxicity assays revealed cytotoxic effects against A549 lung adenocarcinoma cells, indicating anti-proliferative activity against human lung cancer cells. Specifically, the gel containing theophylline (16HAD+Th) exhibited cytotoxicity on cancerous A549 cells with IC 50 values of 19.23±0.6 μg/mL, followed by the gel containing metronidazole (16HAD+Mz) with IC 50 values of 23.75±0.7 μg/mL. Moreover, the system demonstrated comparable antibacterial activity against both gram-negative (E. coli) and gram-positive bacteria (S. aureus)., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The intimate coupling of photocatalysis and biodegradation (ICPB) technology has received much attraction because of the advantages of both photocatalytic reaction and biological treatment. In this study, ZnO-CoFe 2 O 4 @BC (ZCFC) with p-n heterojunction was prepared and used in an ICPB system to degrade metronidazole (MNZ) wastewater. The microstructure, morphology, and optical behavior of heterojunctions in ZCFC were investigated using SEM, XRD, UV-vis, FTIR, and XPS techniques. The results showed that ZCFC inherited the advantages of bamboo biochar's large pore size, and its large pore structure could provide a habitat for bacterial colonization in ICPB, thus shortening the internal mass transfer distance. The degradation of MNZ and chemical oxygen demand (COD) by the ICPB system was 86.8% and 58.5%, respectively, which was superior to single photocatalysis (72.5% for MNZ and 43.8% for COD) and single biodegradation (23.5% for MNZ and 20.1% for COD). In ICPB, photocatalysis and biodegradation showed a synergistic effect in the removal of MNZ, and the order of the major reactive oxygen species (ROS) leading to reduced toxicity of MNZ to the biofilm was •OH > h +  > O 2 • - . High-throughput sequencing analysis showed continuous evolution of biofilm structures in ICPB enriched a variety of functional species, among which the electroactive bacteria Alcaligenes and Brevundimonas played an important role in the degradation of MNZ. In this study, we investigated the possible mechanism of photocatalytic and microbial synergistic degradation of MNZ in the ICPB system and proposed a new technology for degrading antibiotic wastewater that combines the advantages of photocatalysis and biodegradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Antibiotics released into water sources pose significant risks to both human health and the environment. This comprehensive review meticulously examines the ecotoxicological impacts of three prevalent antibiotics-ciprofloxacin, metronidazole, and sulfamethoxazole-on the ecosystems. Within this framework, our primary focus revolves around the key remediation technologies: adsorption and advanced oxidation processes (AOPs). In this context, an array of adsorbents is explored, spanning diverse classes such as biomass-derived biosorbents, graphene-based adsorbents, MXene-based adsorbents, silica gels, carbon nanotubes, carbon-based adsorbents, metal-organic frameworks (MOFs), carbon nanofibers, biochar, metal oxides, and nanocomposites. On the flip side, the review meticulously examines the main AOPs widely employed in water treatment. This includes a thorough analysis of ozonation (O 3 ), the photo-Fenton process, UV/hydrogen peroxide (UV/H 2 O 2 ), TiO 2 photocatalysis, ozone/UV (O 3 /UV), radiation-induced AOPs, and sonolysis. Furthermore, the review provides in-depth insights into equilibrium isotherm and kinetic models as well as prospects and challenges inherent in these cutting-edge processes. By doing so, this review aims to empower readers with a profound understanding, enabling them to determine research gaps and pioneer innovative treatment methodologies for water contaminated with antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bacterial nitroreductase enzymes capable of activating imaging probes and prodrugs are valuable tools for gene-directed enzyme prodrug therapies and targeted cell ablation models. We recently engineered a nitroreductase ( E. coli NfsB F70A/F108Y) for the substantially enhanced reduction of the 5-nitroimidazole PET-capable probe, SN33623, which permits the theranostic imaging of vectors labeled with oxygen-insensitive bacterial nitroreductases. This mutant enzyme also shows improved activation of the DNA-alkylation prodrugs CB1954 and metronidazole. To elucidate the mechanism behind these enhancements, we resolved the crystal structure of the mutant enzyme to 1.98 Å and compared it to the wild-type enzyme. Structural analysis revealed an expanded substrate access channel and new hydrogen bonding interactions. Additionally, computational modeling of SN33623, CB1954, and metronidazole binding in the active sites of both the mutant and wild-type enzymes revealed key differences in substrate orientations and interactions, with improvements in activity being mirrored by reduced distances between the N5-H of isoalloxazine and the substrate nitro group oxygen in the mutant models. These findings deepen our understanding of nitroreductase substrate specificity and catalytic mechanisms and have potential implications for developing more effective theranostic imaging strategies in cancer treatment.

A heterogeneous catalyst was prepared by anchoring spinel cobalt ferrite nanoparticles on porous activated carbon (SCF@AC). The catalyst was tested to activate hydrogen peroxide (HP) in the Fenton degradation of metronidazole (MTZ). SCF nanoparticles were produced through the co-precipitation of iron and cobalt metal salts in an alkaline condition. Elemental mapping, physico-chemical, morphological, structural, and magnetic properties of the as-fabricated catalyst were analyzed utilizing EDX mapping, FESEM-EDS, TEM, BET, XRD, and VSM techniques. The porous structure of AC enhanced the catalytic activity of SCF by a significant decrease in the agglomeration of SCF nanoparticles. The effectiveness of SCF@AC in Fenton degradation improved substantially when UV light and ultrasound (US) irradiations were induced, most likely due to the strong synergistic effect between the catalyst and these irradiation sources. The photo-Fenton system was more efficient than the Fenton, sono-, and sono-photo-Fenton processes eliminating both MTZ and TOC. It was found that AC not only dispersed SCF nanoparticles and improved the stability of the catalyst, but also provided a high adsorption capacity of MTZ, resulting in a faster degradation. After 60 min of the photo-Fenton reaction, the elimination efficiencies of MTZ (30 mg L -1 ) and TOC were 97 and 42.1% under optimum operational conditions (pH = 3.0, HP = 4.0 mM, SCF@AC = 0.3 g L -1 , and UV = 6 W). SCF@AC showed excellent stability with low leaching of metal ions during the reaction. Radical and non-radical (O 2 •- , HO • , and 1 O 2 species), alongside adsorption and photocatalysis mechanisms, were responsible for MTZ decontamination over the SCF@AC/HP/UV system. A comprehensive study on the HP activation mechanism and MTZ degradation pathway was obtained through scavenging tests. The findings demonstrate that SCF@AC is an effective, reusable, and environmentally sustainable catalyst for advanced oxidation processes that can effectively remove organic pollutants from wastewater. This study offers valuable insights into the feasibility of employing SCF@AC catalysts in Fenton-based processes for the degradation of MTZ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The traditional homogenous and heterogenous Fenton reactions have frequently been restrained by the lower production of Fe 2+ ions, which significantly obstructs the generation of hydroxyl radicals from the decomposition of H 2 O 2 . Thus, we introduce novel photo-Fenton-assisted plasmonic heterojunctions by immobilizing Fe 3 O 4 and Bi nanoparticles onto 3D Sb 2 O 3 via co-precipitation and solvothermal approaches. The ternary Sb 2 O 3 /Fe 3 O 4 /Bi composites offered boosted photo-Fenton behavior with a metronidazole (MNZ) oxidation efficiency of 92% within 60 min. Among all composites, the Sb 2 O 3 /Fe 3 O 4 /Bi-5% hybrid exhibited an optimum photo-Fenton MNZ reaction constant of 0.03682 min - 1 , which is 5.03 and 2.39 times higher than pure Sb 2 O 3 and Sb 2 O 3 /Fe 3 O 4 , respectively. The upgraded oxidation activity was connected to the complementary outcomes between the photo-Fenton behavior of Sb 2 O 3 /Fe 3 O 4 and the plasmonic effect of Bi NPs. The regular assembly of Fe 3 O 4 and Bi NPs enhances the surface area and stability of Sb 2 O 3 /Fe 3 O 4 /Bi. Moreover, the limited absorption spectra of Sb 2 O 3 were extended into solar radiation by the Fe 3+ defect of Fe 3 O 4 NPs and the surface plasmon resonance (SPR) effect of Bi NPs. The photo-Fenton mechanism suggests that the co-existence of Fe 3 O 4 /Bi NPs acts as electron acceptor/donor, respectively, which reduces recombination losses, prolongs the lifetime of photocarriers, and produces more reactive species, stimulating the overall photo-Fenton reactions. On the other hand, the photo-Fenton activity of MNZ antibiotics was optimized under different experimental conditions, including catalyst loading, solution pH, initial MNZ concentrations, anions, and real water environments. Besides, the trapping outcomes verified the vital participation of • OH, h + , and • O 2 - in the MNZ destruction over Sb 2 O 3 /Fe 3 O 4 /Bi-5%. In summary, this work excites novel perspectives in developing boosted photosystems through integrating the photocatalysis power with both Fenton reactions and the SPR effects of plasmonic materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis ( T. vaginalis ) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC 50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC 50 values in the nanomolar range and AGR-2 being the most potent (IC 50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis , we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes ( CK , PFK , TPI , and ENOL ) and genes involved in metabolism ( G6PD , TKT , TALDO , NADHOX , ACT , and TUB ), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis .

Metronidazole is a prospective hyperpolarized MRI contrast agent with potential hypoxia sensing utility for applications in cancer, stroke, neurodegenerative diseases, etc. We demonstrate a pilot procedure for production of ∼30 mM hyperpolarized [ 15 N 3 ]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15 N sites achieved in less than 2 min. The 15 N polarization T 1 of ∼12 min is reported for the 15 NO 2 group at the clinically relevant field of 1.4 T in the aqueous phase, demonstrating a remarkably long lifetime of the hyperpolarized state. The produced aqueous solution of [ 15 N 3 ]metronidazole that contained only ∼100 μM of residual Ir was deemed biocompatible via validation through the MTT colorimetric test for assessing cell metabolic activity using human embryotic kidney HEK293T cells. This low-cost and ultrafast hyperpolarization procedure represents a major advance for the production of a biocompatible HP [ 15 N 3 ]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.

The overuse of antibiotics currently results in the presence of various antibiotics being detected in water bodies, which poses potential risks to human health and the environment. Therefore, it is highly significant to remove antibiotics from water. In this study, we developed novel rod-like NiCo-phyllosilicate hybrid catalysts on calcined natural zeolite (NiCo@C-zeolite) via a facile one-pot process. The presence of the zeolite served as both a silicon source and a support, maintaining a high specific surface area of the NiCo@C-zeolite. Remarkably, NiCo@C-zeolite exhibited outstanding catalytic performance in antibiotic degradation under PMS activation. Within just 5 min, the degradation rate of metronidazole (MNZ) reached 96.14%, ultimately achieving a final degradation rate of 99.28%. Furthermore, we investigated the influence of catalyst dosage, PMS dosage, MNZ concentration, initial pH value, and various inorganic anions on the degradation efficiency of MNZ. The results demonstrated that NiCo@C-zeolite displayed outstanding efficacy in degrading MNZ under diverse conditions and maintained a degradation rate of 94.86% at 60 min after three consecutive cycles of degradation. Free radical quenching experiments revealed that SO •- 4 played a significant role in the presence of NiCo@C-zeolite-PMS system. These findings indicate that the novel rod-like NiCo-phyllosilicate hybrid catalysts had excellent performance in antibiotic degradation., (© 2024 IOP Publishing Ltd.)

Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ) 2 AgNO 3 ], [(MTZ) 2 Ag] 2 SO 4 , [Ag(MCZ) 2 NO 3 ], [Ag(MCZ) 2 BF 4 ], [Ag(MCZ) 2 SbF 6 ] and [Ag(MCZ) 2 ClO 4 ] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC 50 values against the A375 line were demonstrated by [Ag(MCZ) 2 NO 3 ] and [(MTZ) 2 AgNO 3 ]. The compound [(MTZ) 2 AgNO 3 ] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.

The objective of the present study was to employ a green synthesis method to produce a sustainable ZnFe 12 O 19 /BiOI nanocomposite and evaluate its efficacy in the photocatalytic degradation of metronidazole (MNZ) from aqueous media. An artificial neural network (ANN) model was developed to predict the performance of the photocatalytic degradation process using experimental data. More importantly, sensitivity analysis was conducted to explore the relationship between MNZ degradation and various experimental parameters. The elimination of MNZ was assessed under different operational parameters, including pH, contaminant concentration, nanocomposite dosage, and retention time. The outcomes exhibited high a desirability performance of the ANN model with a coefficient correlation (R 2 ) of 0.99. Under optimized circumstances, the MNZ elimination efficiency, as well as the reduction in chemical oxygen demand (COD) and total organic carbon (TOC), reached 92.71%, 70.23%, and 55.08%, respectively. The catalyst showed the ability to be regenerated 8 times with only a slight decrease in its photocatalytic activity. Furthermore, the experimental data obtained demonstrated a good agreement with the predictions of the ANN model. As a result, this study fabricated the ZnFe 12 O 19 /BiOI nanocomposite, which gave potential implication value in the effective decontamination of pharmaceutical compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Current study covers the preparation and application of a commercial modified lead oxide battery electrode (LBE) in electrochemical oxidation (ECO) of metronidazole (MNZ) in an aqueous phase. Modified electrode is prepared by doping of bimetal-oxide (Fe and Zn) nanoparticles (NPs) & single metal-oxide (Fe/Zn) on bagasse-waste carbon (bwc) which is further coated on LBE. The modified LBE electrode surface was examined for metal-oxide NPs through X-ray diffraction analysis (XRD). Different electrodes are prepared by varying combinations of two metal-oxide based on molar ratio and tested for electrochemical characterization and MNZ removal test. Based on large oxygen evolution potential in a linear sweep volumetry (LSV) analysis and high MNZ removal rate, the best electrode has been represented as Fe 1 :Co 2 -bwc/LBE which contains Fe & Co molar ratio of 1:2. Moreover, equilibrium attained at faster rate in degradation process of MNZ, where pseudo first order kinetics of 2.29 × 10 -2 min -1 was obtained under optimized condition of (MNZ:100 mg/L, pH:7, CD: 30 mA/cm 2 and electrolyte: 0.05 M Na 2 SO 4 ). Maximum MNZ removal, total organic carbon removal (TOC), mineralization current efficiency (MCE) & energy consumption (EC) of 98.7%, 85.3%, 62.2% & 96.143 kW h/kg-TOC removed are found in 180 min of treatment time for Fe 1 :Co 2 -bwc/LBE electrode. Accelerated service life test confirms that the stability of modified electrode is enhanced by 1.5 times compared to pristine LBE. Repeatability test confirms that modified LBE (Fe 1 :Co 2 -bwc/LBE) can be utilized up to 3 times., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

There are growing concerns about the toxicity of metronidazole (MNZ) antibiotics in wastewater, which must be removed. This study used AgN/MOF-5 (1:3) to investigate the adsorptive removal of MNZ antibiotics from wastewater. Green synthesis of Ag-nanoparticles was from Argemone mexicana leaf aqueous extract blended with the synthesized MOF-5 in 1:3 by proportion. The adsorption materials were characterized by scanning electron microscope (SEM), N 2 adsorption-desorption analysis, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The surface area increased due to the appearance of micropores. Besides, the efficiency of AgN/MOF-5 (1:3) for MNZ removal was evaluated by adsorption properties, including key influential parameters (adsorbent dosage, pH, contact time, etc.) and adsorption mechanism, kinetics/isotherms. The results from the adsorption process conformed to pseudo-second-order kinetics (R 2  = 0.998) and well fitted with the Langmuir isotherm having 191.1 mg/g maximum adsorption capacity. The adsorption mechanism of AgN/MOF-5 (1:3) was due to the interactions of π-π stacking, Ag-N-MOF covalent bonding and hydrogen bonding. Thus, AgN/MOF-5 (1:3) is a potential adsorbent for the removal of aqueous MNZ. The adsorption process is endothermic, spontaneous, and feasible based on the obtained thermodynamic parameter of ΔH O and ΔS O having 14.72 and 0.129 kJ/mol respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Humic acid-based carbon dots (HACDs) have excellent properties and are widely used in environmental detection, bioimaging, and optoelectronic materials. Herein, we investigated the structure-activity relationship between the morphology and optical properties of HACDs, and reported on a novel strategy for metronidazole (MNZ) and ornidazole (ONZ) sensing in multiple real samples. It was found that the average particle size decreased from 3.28 to 2.44 nm, optimal emission wavelength was blue-shifted from 500 to 440 nm, and the quantum yield (QY) improved from 5 to 23% with the temperature increasing from 110 to 400 °C. Under the oxidation of hydrogen peroxide (H 2 O 2 ) and potassium permanganate (KMnO 4 ), the UV-vis spectra of HACD aqueous solution showed time-dependent behavior, and the fluorescence emission of HACDs achieved spectrally tunable multi-color luminescence in the temporal dimension. The surface of HACDs contained a large number of hydroxyl (-OH) and carboxyl (-COOH) fluorophores, resulting in excellent pH sensing. Meanwhile, the synthesized HACDs revealed sensitive response to MNZ and ONZ with the limit of detection (LOD) of 60 nM and 50 nM in aqueous solutions, which had also been successfully applied in various actual samples such as lake water, honey, eggs, and milk with satisfactory results because of the inner filter effect (IFE). Our research is advantageous to enhance the potential applications of HACDs in advanced analytical systems., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet. Thus, the current study aimed to identify anti-cytokine therapeutics for the treatment of COVID-19 patients with cytokine storm. The interaction of MTZ with key cytokines was investigated using molecular docking studies. MTZ-analogues, and its structurally similar FDA-approved drugs were also virtually screened against interleukin-12 (IL-12). Moreover, their mechanism of inhibition regarding IL-12 binding to IL-12 receptor was investigated by measuring the change in volume and area. IL-12-metronidazole complex is found to be more stable than all other cytokines under study. Our study also revealed that the active sites of IL-12 are inhibited from binding to its target, IL-12 receptor, by modifying the position of the methyl and hydroxyl functional groups in MTZ. Three MTZ analogues, metronidazole phosphate, metronidazole benzoate, 1-[1-(2-Hydroxyethyl)-5-nitroimidazol-2-yl]-N-methylmethanimine-oxide, and two FDA-approved drugs acyclovir (ACV), and tetrahydrobiopterin (THB) were also found to prevent binding of IL-12 to IL-12 receptor similar to MTZ by changing the surface and volume of IL-12 upon IL-12-drug/ligand complex formation. According to the RMSD results, after 100 ns MD simulations of human IL-12-MTZ/ACV/THB drug complexes, it was also observed that each complex was swinging within a few Å compared to their corresponding docking poses, indicating that the docking poses were reliable. The current study demonstrates that three FDA-approved drugs, namely, metronidazole, acyclovir and tetrahydrobiopterin, are potential repurposable treatment options for overexpressed serum cytokines found in COVID-19 patients. Similar approach is also useful to develop therapeutics against other human disorders.Communicated by Ramaswamy H. Sarma.

In this study, a novel hydrodynamic cavitation unit combined with a glow plasma discharge system (HC-GPD) was proposed for the degradation of pharmaceutical compounds in drinking water. Metronidazole (MNZ), a commonly used broad-spectrum antibiotic, was selected to demonstrate the potential of the proposed system. Cavitation bubbles generated by hydrodynamic cavitation (HC) can provide a pathway for charge conduction during glow plasma discharge (GPD). The synergistic effect between HC and GPD promotes the production of hydroxyl radicals, emission of UV light, and shock waves for MNZ degradation. Sonochemical dosimetry provided information on the enhanced formation of hydroxyl radicals during glow plasma discharge compared to hydrodynamic cavitation alone. Experimental results showed a MNZ degradation of 14% in 15 min for the HC alone (solution initially containing 300 × 10 -6 mol L -1 MNZ). In experiments with the HC-GPD system, MNZ degradation of 90% in 15 min was detected. No significant differences were observed in MNZ degradation in acidic and alkaline solutions. MNZ degradation was also studied in the presence of inorganic anions. Experimental results showed that the system is suitable for the treatment of solutions with conductivity up to 1500 × 10 -6  S cm -1 . The results of sonochemical dosimetry showed the formation of oxidant species of 0.15 × 10 -3  mol H 2 O 2 L -1 in the HC system after 15 min. For the HC-GPD system, the concentration of oxidant species after 15 min reached 13 × 10 -3  molH 2 O 2 L -1 . Based on these results, the potential of combining HC and GPD systems for water treatment was demonstrated. The present work provided useful information on the synergistic effect between hydrodynamic cavitation and glow plasma discharge and their application for the degradation of antibiotics in drinking water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

We applied gallic acid (GA) as the complexing agent to stabilizing the regeneration of Fe 2+ during the Fe 2+ /peroxydisulfate (PDS) Fenton-like reaction for promoting the removal of metronidazole (MTZ). This research evaluated the elimination of MTZ by optimizing the dose of GA and Fe 2+ and pH condition. MTZ removal reached 83% at the GA: Fe 2+ molar ratio of 1:1 (30 μM) and initial pH 5 and 6.2 after 120 min, and the kinetics showed two degradation phases (k obs1  = 0.09636 for the rapid stage and k obs2  = 0.01056 for the slow stage). The Fe 2+ and GA complexes could expand the range of pH applicability and effectively stabilize the regeneration of Fe 2+ , which ultimately promoted the decontamination of MTZ. Sulfate radical (SO 4 .- ), hydroxyl radicals, and singlet oxygen were proved to exist in this ternary system and contribute to MTZ removal, and SO 4 .- played the dominant role. Furthermore, the possible pathways and mechanisms for MTZ degradation were proposed, and the simulation result indicated that the toxicity of degradation intermediates of MTZ were declined. The GA assisted Fe 2+ /PDS system provided an improved promising advanced oxidation process for organic wastewater disposal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death, creating difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide, Ca(OH) 2 ), and (2) coat the electrospun fibrous gutta-percha (GP) cones., Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicament concentrations. Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS) were carried out to investigate fiber morphology and antibiotic incorporation, and characterize GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were determined via fourier transform infrared spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method., Results: The mean fiber diameter of the experimental groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared to the negative control and PVP., Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Ca(OH) 2 )-NFs coated GP cones have significant potential in eliminating intracanal bacteria, having cell-friendly behavior and clinical usage features., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Metronidazole (MNZ) is a nitroimidazole derivative antibiotic that has been generally used in the treatment of rosacea. However, it has low molecular weight and lipophilicity, limiting the effectiveness of MNZ in the topical treatment of rosacea. This study reports an MNZ-loaded solid lipid microparticle (SLM) gel formulation with sustained drug release effects required in the treatment of rosacea. SLM was formulated using the double emulsification method with five different concentrations of glyceryl monostearate (GMS) as a solid lipid used to encapsulate MNZ. All the MNZ-loaded SLM formulas were extensively characterized by various analytical tools. After optimized MNZ-loaded SLM formulation was obtained, then formulated into gel preparation. To obtain a gel formula with good physical characteristics and drug release in the development of topical therapy, the SLM-loaded gel was further evaluated, covering various parameters such as pH, viscosity, rheology, spreadability, extrudability, skin occlusivity, gel strength, permeation and retention ex vivo, as well as hemolysis tests and antioxidant activity. The evaluation results showed that the SLM formulations had desired properties with optimum encapsulation efficiency. Moreover, the gels prepared from carbomer possessed desired characteristics and were found to be hemocompatible. In addition, the gel formula with a carbomer concentration of 1.25 % can provide better drug release with the highest MNZ retention after 24 h of 2.35 ± 0.05 mg. Notably, the formulation of MNZ into SLM and hydrogel did not affect the antioxidant activity. Thus, it can provide continuous drug release, which could potentially be useful in increasing efficacy in rosacea therapy. The results obtained also showed a significant difference (p < 0.05) compared to the control formula and other formulas. Therefore, this study has proven a new approach to developing drug delivery systems for rosacea treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A polymer-TiO 2 macro composite (i.e., PVA-CS-TiO 2 ) was synthesized via chemical precipitation of PVA-CS-TiO 2 blend in alkali/solvent medium and applied for the removal of three model antibiotics (i.e., metronidazole (MNZ), ceftiofur (CEF) and tetracycline (TET)), as single compound and multi-compound conditions. The photocatalytic and adsorptive removals of antibiotics (concentrations of 0.1, 1 and 10 mg L -1 ) by the composite in an UV reactor system (32 W UV-C power, 0.3 g L -1 of composite) was assessed through kinetic models. Antibiotics adsorption followed pseudo-second-order kinetics, and the order of adsorption was MNZ > TET > CEF. On the other hand, the hydrophilic MNZ was degraded faster compared to hydrophobic CEF and TET drugs. Moreover, UV reactor system exhibited antagonistic behavior under multi-compound condition. Micro-toxicity of antibiotics was performed using bioluminescent bacterium Vibrio fischeri and EC 50 of CEF, TET and MNZ were found to be 18.25 mg L -1 , 173.8 mg L -1 , and 668.6 mg L -1 , respectively. However, the relative toxicity levels of PVA-CS-TiO 2 and treated effluent were well with the limits as inferred from the microtoxicity analysis. Thus, synthesized biocompatible composite exhibited structural stability, consistent performance for three photocatalytic cycles for all antibiotics at a minimal catalyst loading, easily retained using metallic tea strainer and does not exhibit microtoxicity has a scope for real-time applications.

Metronidazole in aqueous solution is sensitive to light and UV irradiation, leading to the formation of N-(2-hydroxyethyl)-5-methyl-l,2,4-oxadiazole-3-carboxamide. This is revealed here by liquid chromatography with tandem photo diode array detection and mass spectrometry (LC-PDA-MS) and further verified by comparison with the corresponding reference substance and proton nuclear magnetic resonance ( 1 H-NMR). However, in current compendial tests for related substances/organic impurities of metronidazole, the above photolytic degradant could not be detected. Thus, when photodegradation of metronidazole occurs, it could not be demonstrated. In our study, an improved LC method was developed and validated, which includes a detection at a wavelength of 230 nm and optimization of mobile phase composition thereby a better separation was obtained., (© 2022. The Author(s).)

The identification of novel compounds that can inhibit physiologically and metabolically important drug targets or enzymes has prime importance in medicinal chemistry. With this aim, a range of secnidazole esters 1-30 were synthesized under the heading of biology-oriented drug synthesis by the 1,1'-carbonyldiimidazole-mediated coupling reaction between secnidazole and varyingly benzoic acid derivatives. All compounds were screened for inhibitory activity against human carbonic anhydrase (hCA) I and II, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The results indicate that all the synthesized compounds showed potent inhibitory activities against all targets, as compared to the standard inhibitors, revealed by IC 50 values. K i values of the secnidazole derivatives 1-30 for hCA I, hCA II, AChE, BChE, and α-glucosidase enzymes were obtained in the ranges of 47.37-190.74, 44.38-198.21, 12.14-68.37, 8.04-61.53, and 7.78-45.91 nM, respectively. To assess the enzyme-ligand interactions, the optimized most active compounds 2, 3, 8, 9, 14, 17, and 23 were subjected to molecular docking studies with modeled AChE, BChE, hCA I, hCA II, and α-glucosidase enzymes, where several important and key interactions were monitored with amino acid residues of each target enzyme., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

In this study, a combination therapy of several natural products was evaluated in vivo in the Giardia duodenalis infection model. G. duodenalis infected mice were treated as follows: distilled water (infected control C+), BIOintestil® (BIO; natural products of Cymbopogon martinii and Zingiber officinale), MicrobiomeX® (MBX; extract of Citrus sinensis and Citrus paradisi), MBX + BIO, Camellia sinensis tea (CPR; black tea). These natural compounds were administered in a dose of 100 mg/day and were compared to G. duodenalis-infected mice treated with albendazole (ALB; 50 mg/Kg/day) and metronidazole (MET; 500 mg/Kg/day), the conventional therapies used to this day. One group remained un-infected and untreated as our control group (C-). Treatment started 8 days after infection, and after 5 days of treatment (7 days for MET), all animals were followed for 15 days. We continuously checked for the presence of G. duodenalis by Faust method, in association with detection of the parasite by PCR from feces, as well for the presence of trophozoites in the intestinal mucosa after sacrifice. Animals treated with MBX, BIO and MBX + BIO presented an undetectable parasitic load until the 15th day of monitoring, while animals treated with CPR, MET and ALB continued to release cysts. Animals in the MBX, MBX + BIO, ALB groups consumed lower feed, MBX, CPR, MET had greater weight and MBX, MBX + BIO, BIO, CPR, C- consumed more water when compared to infected-group control. MBX and BIO alone or associated eliminated G. duodenalis without apparent adverse effects and animals of these groups showed better clinical performance in relation to those with high parasitic load. MET, ALB and CPR only decreased the number of cysts, indicating limitations and therapeutic failure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study aimed at engineering cytocompatible and injectable antibiotic-laden fibrous microparticles gelatin methacryloyl (GelMA) hydrogels for endodontic infection ablation. Clindamycin (CLIN) or metronidazole (MET) was added to a polymer solution and electrospun into fibrous mats, which were processed via cryomilling to obtain CLIN- or MET-laden fibrous microparticles. Then, GelMA was modified with CLIN- or MET-laden microparticles or by using equal amounts of each set of fibrous microparticles. Morphological characterization of electrospun fibers and cryomilled particles was performed via scanning electron microscopy (SEM). The experimental hydrogels were further examined for swelling, degradation, and toxicity to dental stem cells, as well as antimicrobial action against endodontic pathogens (agar diffusion) and biofilm inhibition, evaluated both quantitatively (CFU/mL) and qualitatively via confocal laser scanning microscopy (CLSM) and SEM. Data were analyzed using ANOVA and Tukey's test (α = 0.05). The modification of GelMA with antibiotic-laden fibrous microparticles increased the hydrogel swelling ratio and degradation rate. Cell viability was slightly reduced, although without any significant toxicity (cell viability > 50%). All hydrogels containing antibiotic-laden fibrous microparticles displayed antibiofilm effects, with the dentin substrate showing nearly complete elimination of viable bacteria. Altogether, our findings suggest that the engineered injectable antibiotic-laden fibrous microparticles hydrogels hold clinical prospects for endodontic infection ablation.

Self-assembly of two Zn-MOFs, [Zn 2 L(DMF) 3 ] · H 2 O·5DMF (1) and [Zn 2 L(H 2 O) 2 ] · 4H 2 O·3DMF (2), was achieved with an amide-functionalized tetracarboxylate ligand under similar conditions. Incorporated amide groups make the tetratopic linkers exhibit different configurations, tetrahedron and square, and subsequently combine tetrahedral [Zn 2 (CO 2 ) 4 ] clusters or square paddle-well [Zn 2 (CO 2 ) 4 ] clusters to afford a lon net for 1 and a nbo net for 2. Remarkably, 2 demonstrated high porosity and amide group decorated cages, and thereby proved to be a good capturing agent for a fluorescent dye molecule (DMASM). Consequently, a dual-emitting DMASM@2 sensor was successfully fabricated based on effective energy transfer from the host framework to DMASM with the variable luminescent color being visible to the naked eye. DMASM@2 could be used for the detection of metronidazole (MDZ) and dimetridazole (DTZ) with high sensitivity and remarkable recyclability.

Local delivery of drug is a promising strategy to manage periodontitis characterized by chronic inflammation of the soft tissue surrounding the teeth. An optimized system should prolong the drug retention time and exhibit controlled drug permeation through the buccal mucosal layer. This study was aimed to develop hydroxyethyl cellulose (HEC)-based gel containing metronidazole (MTZ) loaded in solid lipid nanoparticles (SLNs), and to enhance the antimicrobial activity of MTZ. SLNs were prepared using a combination method of solvent evaporation and hot homogenization. The results showed that the fabricated SLNs, comprising of Precirol (2.93%, w/v), Tween 80 (1.8%, w/v), and the drug:lipid ratio of 19.3% (w/w), were approximately 200 nm in size, with a narrow distribution. The HEC (3%, w/w)-based gel formed a smooth, homogeneous structure and had preferable mechanical and rheological properties. Moreover, the MTZ-loaded SLNs-based HEC gel (equivalent to 1% of MTZ, w/w) exhibited a sustained in vitro drug release pattern, optimal ex vivo permeability, and enhanced in vitro antimicrobial activity after 24 h of treatment. These findings indicate the potential of the MTZ-loaded SLNs-based HEC formulation for local drug delivery at the buccal mucosa in managing periodontal disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Metronidazole (MET) is a commonly detected contaminant in the environment. The compound is classified as poorly biodegradable and highly soluble in water. Heterogeneous photocatalysis is the most promoted water purification method due to the possibility of using sunlight and small amounts of a catalyst needed for the process. The aim of this study was to select conditions for photocatalytic removal of metronidazole from aquatic samples. The effect of catalyst type, mass, and irradiance intensity on the efficiency of metronidazole removal was determined. For this purpose, TiO 2 , ZnO, ZrO 2 , WO 3 , PbS, and their mixtures in a mass ratio of 1:1 were used. In this study, the transformation products formed were identified, and the mineralization degree of compound was determined. The efficiency of metronidazole removal depending on the type of catalyst was in the range of 50-95%. The highest MET conversion (95%) combined with a high degree of mineralization (70.3%) was obtained by using a mixture of 12.5 g TiO 2 -P25 + PbS (1:1; v / v ) and running the process for 60 min at an irradiance of 1000 W m -2 . Four MET degradation products were identified by untargeted analysis, formed by the rearrangement of the metronidazole and the C-C bond breaking.

Due to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescence spectroscopic measurements gave 1.9 × 10 5 M -1 and 1.0 × 10 4 M -1 as the association constants of the protonated metronidazole inclusion in CB7 and SCX4, whereas the unprotonated guests had values more than one order of magnitude lower, respectively. The preferential binding of the protonated metronidazole resulted in 1.91 pH unit pK a diminution upon encapsulation in CB7, but the complexation with SCX4 led to a pK a decrease of only 0.82 pH unit. The produced protonated metronidazole-SCX4 complex induced nanoparticle formation with protonated chitosan by supramolecular crosslinking of the polysaccharide chains. The properties of the aqueous nanoparticle solutions and the micron-sized solid composite produced therefrom by nano spray drying were unraveled. The results of the present work may find application in the rational design of tailor-made self-assembled drug carrier systems.

Mucoadhesive buccal patch is a promising dosage form for a successful oral drug delivery, which provides unique advantages for various applications such as treatment of periodontal disease and postdental surgery disorders. The aim of this study is to synthesize a novel multifunctional mucoadhesive buccal patch in a multilayer reservoir design for therapeutic applications. The patches were fabricated through simultaneous electrospinning of chitosan/poly(vinylalcohol) (PVA)/ibuprofen and electrospraying of phenylalanine amino acid nanotubes (PhNTs) containing metronidazole into the electrospun mats through a layer-by-layer process. An electrospun poly(caprolactone) (PCL) was used as an impermeable backing layer to protect the mucoadhesive component from tongue movement and drug loss. Buccal patches were characterized using scanning electron microscopy (SEM) and field emission scanning electron microscopy (FESEM) and also evaluated in terms of physicomechanical parameters such as pH, weight, thickness, tensile strength, folding endurance, and mucoadhesive properties. The swelling index of the patches was examined with respect to the PVA/chitosan ratio. The effect of genipin addition to the electrospinning solution was also studied on mucoadhesive and swelling properties. The cell viability of buccal patches was assessed by methylthiazolydiphenyl-tetrazolium bromide test on L929 fibroblast cell line. The patch with an optimal amount of mucoadhesive polymers (PVA/chitosan 80:20) and crosslinking agent (0.05 g) indicated an ideal hemostatic activity along with antibacterial properties against Streptococcus mutans bacteria. The synthesized multifunctional mucoadhesive patch with a novel composition and design has a great potential for oral therapeutic applications., (© 2021 Wiley Periodicals LLC.)

Gingivitis is a condition that needs sustained concentration of antibiotic locally over extended period of time. The current study aimed to formulate and evaluate the sustained and localized release of metronidazole (MTZ) as mucoadhesive buccal tablet containing hydroxypropylmethyl cellulose (HPMC), Carbopol 940® (CP), carboxymethylcellulose (CMC) and ethyl cellulose (EC) as mucoadhesive polymers. Tablets were directly compressed with proportions of polymeric blends (F1-F16). The results indicated that weight variation (249±2.10mg) and friability (0.21%) were within USP compendial limits. Maximum mucoadhesive strength and time were depicted by F1 and F14 which were 28.47g and 12hr respectively. Formulations, except F4, were within physiological pH limit. Maximum swellability index (261.9%) was exhibited by F16, at 8 hr, containing highest concentration of CP, HPMC and additional CMC. For in vitro release, the pre-set 8 hr complete release were shown by formulations, F15 and F16 which were 100% and 97%, respectively. Genetic algorithm was applied on the attributes to optimize polymeric response in accordance with desirability. The software predicted composition (F17) was tested which revealed that physical characteristics were in accordance with the compendial standards. The release kinetics, evaluated through DDsolver⌖, suggested that release of MTZ followed non-Fickian diffusion type in Korsmeyer-Peppas model. Therefore, MTZ, if delivered as mucoadhesive buccal formulation (F17) containing amounts (mg) of CP (16.4), HPMC (78.7), CMC (8.3) and EC (10.5) will simulate satisfactory release i.e. 96% at 8 hr in simulated buccal fluid.

Bacterial vaginosis is a prevalent women's health issue that affects millions of women worldwide every year; however, current treatments are often messy, inconvenient, and ineffective. Therefore, we developed a new hyaluronic acid-based film to deliver metronidazole that would be more effective, more convenient, and at a pH similar to that of the normal vaginal environment. Films were made by crosslinking modified hyaluronic acid to create a hydrogel, in which metronidazole or metronidazole benzoate and methylcellulose were incorporated, and the hydrogel was dried to a thin film. Through release testing, coupled with assessments of handleability, tensile strength, and mucoadhesion, it was determined that the films have the potential to remain in the vaginal environment for an extended time period and gradually release the drug for at least 6 days, which is a typical treatment length. As such, the films present a viable alternative to current treatment methods, allowing for both easy handling and a single treatment while eliminating the issues of pH and overall inconvenience., (© 2021 Wiley Periodicals LLC.)

Periodontitis compromises the integrity and function of tooth-supporting structures. Although therapeutic approaches have been offered, predictable regeneration of periodontal tissues remains intangible, particularly in anatomically complex defects. In this work, personalized and defect-specific antibiotic-laden polymeric scaffolds containing metronidazole (MET), tetracycline (TCH), or their combination (MET/TCH) were created via electrospinning. An initial screening of the synthesized fibers comprising chemo-morphological analyses, cytocompatibility assessment, and antimicrobial validation against periodontopathogens was accomplished to determine the cell-friendly and anti-infective nature of the scaffolds. According to the cytocompatibility and antimicrobial data, the 1:3 MET/TCH formulation was used to obtain three-dimensional defect-specific scaffolds to treat periodontally compromised three-wall osseous defects in rats. Inflammatory cell response and new bone formation were assessed by histology. Micro-computerized tomography was performed to assess bone loss in the furcation area at 2 and 6 weeks post implantation. Chemo-morphological and cell compatibility analyses confirmed the synthesis of cytocompatible antibiotic-laden fibers with antimicrobial action. Importantly, the 1:3 MET/TCH defect-specific scaffolds led to increased new bone formation, lower bone loss, and reduced inflammatory response when compared to antibiotic-free scaffolds. Altogether, our results suggest that the fabrication of defect-specific antibiotic-laden scaffolds holds great potential toward the development of personalized ( i.e. , patient-specific medication) scaffolds to ablate infection while affording regenerative properties.

We demonstrate the suitability of a fast, green, easy-to-perform, and modified sample extraction procedure, i.e., dispersive liquid-liquid microextraction (DLLME) for the determination of efavirenz (EFV) in human plasma. Data acquisition was done by gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring (SIM) mode. The simplicity of the method lies in, among others, the avoidance of the use of large organic solvent volumes as mobile phases and non-volatile buffers that tend to block the plumbing in high-performance liquid chromatography (HPLC). Chromatographic and mass spectral parameters were optimized using bovine whole blood for matrix matching due to insufficient human plasma. Method validation was accomplished using the United States Food and Drug Administration (USFDA) 2018 guidelines. The calibration curve was linear with a dynamic range of 0.10-2.0 μg/mL and an R 2 value of 0.9998. The within-run accuracy and precision were both less than 20% at the lower limit of quantification (LLOQ) spike level. The LLOQ was 0.027 μg/mL which compared well with some values but was also orders of magnitude better than others reported in the literature. The percent recovery was 91.5% at the LLOQ spike level. The DLLME technique was applied in human plasma samples from patients who were on treatment with EFV. The human plasma samples gave concentrations of EFV ranging between 0.14-1.00 μg/mL with three samples out of seven showing concentrations that fell within or close to the recommended therapeutic range., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Imidazole has anti-inflammatory, antituberculotic, antimicrobial, antimycotic, antiviral, and antitumor properties in the human body, to name a few. Metronidazole [1-(2-Hydroxyethyl)-2-methyl-5-nitroimidazole] is a widely used antiprotozoan and antibacterial medication. Using fourier transform infrared spectroscopy, the current study models the antibacterial activity of already synthesised Metronidazole (MTZ) complexes ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]) against E. coli, B. bronceptica, S. epidermidis, B. pumilus and S. aureus. To characterise the Metronidazole complexes for antibacterial activity against 05 microbes, the least angular regression and least absolute shrinkage selection operators were used. Asymmetric Least Squares was used to correct the spectrum baseline. Least angular regression outperforms cross-validated root mean square error in the fitted models. Using Least angular regression, influential wavelengths that explain the variation in antibacterial activity of Metronidazole complexes were identified and mapped against functional groups., (© 2021. The Author(s).)