15N Hyperpolarization of Metronidazole Antibiotic in Aqueous Media Using Phase-Separated Signal Amplification by Reversible Exchange with Parahydrogen.

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 [15N3]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15N sites achieved in less than 2 min. The 15N polarization T1 of ∼12 min is reported for the 15NO2 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 [15N3]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 [15N3]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.

Metronidazole degradation mechanism by sono-photo-Fenton processes using a spinel ferrite cobalt on activated carbon catalyst.

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 (O2•-, HO•, and 1O2 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.

Mesoporous cobalt-manganese layered double hydroxides promote the activation of calcium sulfite for degradation and detoxification of metronidazole.

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 (CoxMny-LDH) with abundant oxygen vacancies (Ov) were successfully synthesized using the co-precipitation method and used to activate calcium sulfite (CaSO3) with slight soluble in water for MNZ degradation. The characterization results revealed that Co2Mn-LDH had higher specific areas and exhibited good crystallinity. Co2Mn-LDH/CaSO3 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 SO4•- and 1O2 played pivotal roles in the MNZ degradation process by activated CaSO3, while the redox cycles of Co2+/Co3+ and Mn3+/Mn4+ 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 Co2Mn-LDH/CaSO3 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.

One-pot synthesis of NiCo-phyllosilicate supported on zeolite for enhanced degradation of antibiotic contaminants.

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•-4played 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.

Photocatalytic decomposition of metronidazole by zinc hexaferrite coated with bismuth oxyiodide magnetic nanocomposite: Advanced modelling and optimization with artificial neural network.

The objective of the present study was to employ a green synthesis method to produce a sustainable ZnFe12O19/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 (R2) 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 ZnFe12O19/BiOI nanocomposite, which gave potential implication value in the effective decontamination of pharmaceutical compounds.

Bimetal-oxide (Fe/Co) modified bagasse-waste carbon coated on lead oxide-battery electrode for metronidazole removal.

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 Fe1:Co2-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/cm2 and electrolyte: 0.05 M Na2SO4). 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 Fe1:Co2-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 (Fe1:Co2-bwc/LBE) can be utilized up to 3 times.

Green synthesis of Ag nanoparticles from Argemone mexicana L. leaf extract coated with MOF-5 for the removal of metronidazole antibiotics from aqueous solution.

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), N2 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 (R2 = 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 ΔHO and ΔSO having 14.72 and 0.129 kJ/mol respectively.

Simultaneous hydrodynamic cavitation and glow plasma discharge for the degradation of metronidazole in drinking water.

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 H2O2 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 molH2O2L-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.

Promoted elimination of metronidazole in ferrous ions activated peroxydisulfate process by gallic acid complexation.

We applied gallic acid (GA) as the complexing agent to stabilizing the regeneration of Fe2+ during the Fe2+/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 Fe2+ and pH condition. MTZ removal reached 83% at the GA: Fe2+ molar ratio of 1:1 (30 µM) and initial pH 5 and 6.2 after 120 min, and the kinetics showed two degradation phases (kobs1 = 0.09636 for the rapid stage and kobs2 = 0.01056 for the slow stage). The Fe2+ and GA complexes could expand the range of pH applicability and effectively stabilize the regeneration of Fe2+, which ultimately promoted the decontamination of MTZ. Sulfate radical (SO4.-), hydroxyl radicals, and singlet oxygen were proved to exist in this ternary system and contribute to MTZ removal, and SO4.- 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 Fe2+/PDS system provided an improved promising advanced oxidation process for organic wastewater disposal.

Novel Electrospun Polymeric Nanofibers Loaded Different Medicaments as Drug Delivery Systems for Regenerative Endodontics.

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.

Metronidazole, acyclovir and tetrahydrobiopterin may be promising to treat COVID-19 patients, through interaction with interleukin-12.

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.

Spectrally tunable humic acid-based carbon dots: a simple platform for metronidazole and ornidazole sensing in multiple real samples.

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 (H2O2) and potassium permanganate (KMnO4), 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.

Enhanced skin localization of metronidazole using solid lipid microparticles incorporated into polymeric hydrogels for potential improved of rosacea treatment: An ex vivo proof of concept investigation.

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.

Photocatalytic and adsorptive performance of polyvinyl alcohol/chitosan/TiO2 composite for antibiotics removal: single- and multi-pollutant conditions.

A polymer-TiO2 macro composite (i.e., PVA-CS-TiO2) was synthesized via chemical precipitation of PVA-CS-TiO2 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 EC50 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-TiO2 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.

Identification of the major photodegradant in metronidazole by LC-PDA-MS and its reveal in compendial methods.

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 (1H-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.

Engineering of Injectable Antibiotic-laden Fibrous Microparticles Gelatin Methacryloyl Hydrogel for Endodontic Infection Ablation.

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.

Elimination of Giardia duodenalis BIV in vivo using natural extracts in microbiome and dietary supplements.

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.

A dye encapsulated zinc-based metal-organic framework as a dual-emission sensor for highly sensitive detection of antibiotics.

Self-assembly of two Zn-MOFs, [Zn2L(DMF)3]·H2O·5DMF (1) and [Zn2L(H2O)2]·4H2O·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 [Zn2(CO2)4] clusters or square paddle-well [Zn2(CO2)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.

Biology-oriented drug synthesis and evaluation of secnidazole esters as novel enzyme inhibitors.

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 IC50 values. Ki 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.

Formulation and characterization of hydroxyethyl cellulose-based gel containing metronidazole-loaded solid lipid nanoparticles for buccal mucosal drug delivery.

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.