Mechanochemically Induced Solid-State Transformations of Levofloxacin.

Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone drug that exists in both hydrated and anhydrous/dehydrated forms. Due to the complexity of such a compound, the primary aim of this study was to investigate the amorphization capabilities and solid-state transformations of LVXh when exposed to mechanical treatment using ball milling. Spray drying was utilized as a comparative method for investigating the capabilities of complete LVX amorphous (LVXam) formation. The solid states of the samples produced were comprehensively characterized by powder X-ray diffraction, thermal analysis, infrared spectroscopy, Rietveld method, and dynamic vapor sorption. The kinetics of the process and the quantification of phases at different time points were conducted by Rietveld refinement. The impact of the different mills, milling conditions, and parameters on the composition of the resulting powders was examined. A kinetic investigation of samples produced using both mills disclosed that it was in fact possible to partially amorphize LVXh upon mechanical treatment. It was discovered that LVXh first transformed to the anhydrous/dehydrated form γ (LVXγ), as an intermediate phase, before converting to LVXam. The mechanism of LVXam formation by ball milling was successfully revealed, and a new method of forming LVXγ and LVXam by mechanical forces was developed. Spray drying from water depicted that complete amorphization of LVXh was possible. The amorphous form of LVX had a glass transition temperature of 80 °C. The comparison of methods highlighted that the formation of LVXam is thus both mechanism- and process-dependent. Dynamic vapor sorption studies of both LVXam samples showed comparable stability properties and crystallized to the most stable hemihydrate form upon analysis. In summary, this work contributed to the detailed understanding of solid-state transformations of essential fluoroquinolones while employing greener and more sustainable manufacturing methods.

Multifunctional Fe/Cu Dual-Single Atom Nanozymes with Enhanced Peroxidase Activity for Isoniazid Detection and Levofloxacin Degradation.

The design of single-atom nanozymes with dual active sites to increase their activity and for the detection and degradation of contaminants is rare and challenging. In this work, a single-atom nanozyme (FeCu-NC) based on a three-dimensional porous Fe/Cu dual active site was developed as a colorimetric sensor for both the quantitative analysis of isoniazid (INH) and the efficient degradation of levofloxacin (LEV). FeCu-NC was synthesized using a salt template and freeze-drying method with a three-dimensional hollow porous structure and dual active sites (Fe-Nx and Cu-Nx). In terms of morphology and structure, FeCu-NC exhibits excellent peroxidase-like activity and catalytic properties. Therefore, a colorimetric sensor was constructed around FeCu-NC for sensitive and rapid quantitative analysis of INH with a linear range of 0.9-10 µM and a detection limit as low as 0.3 µM, and the sensor was successfully applied to the analysis of INH in human urine. In addition, FeCu-NC promoted the efficient degradation of LEV by peroxymonosulfate activation, with a degradation rate of 90.4% for LEV at 30 min. This work sheds new light on the application of single-atom nanozymes to antibiotics for colorimetric sensing and degradation.

Preparation of Zn/Zr-MOFs by microwave-assisted ball milling and adsorption of lomefloxacin hydrochloride and levofloxacin hydrochloride in wastewater.

The Zn/Zr-MOFs were synthesized via microwave-assisted ball milling and subsequently characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The thermal stability of the Zn/Zr-MOFs was evaluated through thermogravimetry (TGA). The results demonstrated the exceptional adsorption properties of the Zn/Zr-MOFs towards Lomefloxacin hydrochloride and Levofloxacin hydrochloride. At a concentration of 30 ppm for Lomefloxacin hydrochloride, the addition of 30 mg of Zn/Zr-MOFs material resulted in an adsorption capacity of 179.2 mg•g-1. Similarly, at a concentration of 40 ppm for Levofloxacin hydrochloride, the addition of 30 mg Zn/Zr-MOFs material led to an adsorption capacity of 187.1 mg•g-1. Kinetic analysis revealed that the experimental data aligned well with a pseudo-second order kinetic model. Overall, these findings highlight the significant potential application of Zn/Zr-MOF materials in wastewater treatment.

UPLC/Q-TOF-MS-based metabolomics and molecular docking analysis of Bifidobacterium adolescentis exposure to levofloxacin.

Antibiotic-associated diarrhea is a common adverse reaction caused by the widespread use of antibiotics. The decrease in probiotics is one of the reasons why antibiotics cause drug-induced diarrhea. However, few studies have addressed the intrinsic mechanism of antibiotics inhibiting probiotics. To investigate the underlying mechanism of levofloxacin against Bifidobacterium adolescentis, we used a metabolomics mass spectrometry-based approach and molecular docking analysis for a levofloxacin-induced B. adolescentis injury model. The results showed that levofloxacin reduced the survival rate of B. adolescentis and decreased the number of B. adolescentis. The untargeted metabolomics analysis identified 27 potential biomarkers, and many of these metabolites are involved in energy metabolism, amino acid metabolism and the lipid metabolism pathway. Molecular docking showed that levofloxacin can bind with aminoacyl-tRNA synthetase and lactic acid dehydrogenase. This result provides a novel insight into the mechanism of the adverse reactions of levofloxacin.

Degradation of levofloxacin using electro coagulation residuals-alginate beads as a novel heterogeneous electro-fenton composite.

The presence of levofloxacin (LEV) in aqueous solutions can pose health risks to humans, have adverse effects on aquatic organisms and ecosystems, and contribute to the development of antibiotic-resistant bacteria. This study aims to investigate the feasibility of using electrocoagulation residuals (ECRs) as a heterogeneous catalyst in the electro-Fenton process for degrading LEV. By combining electrocoagulation residuals with sodium alginate, ECRs-alginate beads were synthesized as a heterogeneous electro-Fenton composite. The response surface method was employed to investigate the optimization and influence of various operating parameters such as the initial concentration of LEV (10-50 mg/L), voltage (15-35 V), pH (3-9), and catalyst dose (1-9 g/L). The successful incorporation of iron and other metals into the ECRs-alginate beads was confirmed by characterization tests such as EDX and FTIR. By conducting a batch reaction under optimal conditions (initial LEV concentration = 20 mg/L, pH = 4.5, voltage = 30V, and catalyst dose = 7 g/L), a remarkable degradation of 99% for LEV was achieved. Additionally, under these optimal conditions, a high removal efficiency of 92.3% for total organic carbon (TOC) could be attained within 120 min and these findings are remarkable compared to previous studies. The results further indicated that the degradation of levofloxacin (LEV) could be accurately quantified by utilizing the first-order kinetic reaction with a 0.03 min-1 rate constant. The synthesized beads offered notable advantages in terms of being eco-friendly, simple to use, highly efficient, and easily recoverable from the liquid medium after use.

A novel molecularly imprinted electrochemical sensor from poly (3, 4-ethylenedioxythiophene)/chitosan for selective and sensitive detection of levofloxacin.

The improper usage of levofloxacin (LEV) endangers both environmental safety and human public health. Therefore, trace analysis and detection of LEV have extraordinary significance. In this paper, a novel molecularly imprinted polymer (MIP) electrochemical sensor was developed for the specific determination of LEV by electrochemical polymerization of o-phenylenediamine (o-PD) using poly(3,4-ethylenedioxythiophene)/chitosan (PEDOT/CS) with a porous structure and rich functional groups as a carrier and LEV as a template molecule. The morphology, structure and properties of the modified materials were analyzed and studied. The result showed that the electron transfer rate and the electroactive strength of the electrode surface are greatly improved by the interconnection of PEDOT and CS. Meanwhile, PEDOT/CS was assembled by imprinting with o-PD through non-covalent bonding, which offered more specific recognition sites and a larger surface area for the detection of LEV and effectively attracted LEV through intermolecular association. Under the optimized conditions, MIP/PEDOT/CS/GCE showed good detection performance for LEV in a wide linear range of 0.0019- 1000 µM, with a limit of detection (LOD, S/N = 3) of 0.4 nM. Furthermore, the sensor has good stability and selectivity, and exhibits excellent capabilities in the microanalysis of various real samples.

Application of machine learning in the study of cobalt-based oxide catalysts for antibiotic degradation: An innovative reverse synthesis strategy.

This study addresses antibiotic pollution in global water bodies by integrating machine learning and optimization algorithms to develop a novel reverse synthesis strategy for inorganic catalysts. We meticulously analyzed data from 96 studies, ensuring quality through preprocessing steps. Employing the AdaBoost model, we achieved 90.57% accuracy in classification and an R²value of 0.93 in regression, showcasing strong predictive power. A key innovation is the Sparrow Search Algorithm (SSA), which optimizes catalyst selection and experimental setup tailored to specific antibiotics. Empirical experiments validated SSA's efficacy, with degradation rates of 94% for Levofloxacin and 97% for Norfloxacin, aligning closely with predictions within a 2% margin of error. This research advances theoretical understanding and offers practical applications in material science and environmental engineering, significantly enhancing catalyst design efficiency and accuracy through the fusion of advanced machine learning techniques and optimization algorithms.

Highly stable Ag-doped Cu2O immobilized cellulose-derived carbon beads with enhanced visible-light photocatalytic degradation of levofloxacin.

Ag-doped Cu2O immobilized carbon beads (Ag/Cu2O@CB) based composite photocatalysts have been prepared for the removal of levofloxacin, an antibiotic, from water. The photocatalysts were prepared by the processes of chemical reduction and in-situ solid-phase precipitation. The composite photocatalyst was characterized by a porous and interconnected network structure. Ag nanoparticles were deposited on Cu2O particles to develop a metal-based semiconductor to increase the catalytic efficiency of the system and the separation efficiency of the photogenerated carriers. Cellulose-derived carbon beads (CBs) can also be used as electron storage libraries which can capture electrons released from the conduction band of Cu2O. The results revealed that the maximum catalytic degradation efficiency of the composite photocatalyst for the antibiotic levofloxacin was 99.02 %. The Langmuir-Hinshelwood model was used to study the reaction kinetics, and the process of photodegradation followed first-order kinetics. The maximum apparent rate was recorded to be 0.0906 min-1. The mass spectrometry technique showed that levofloxacin degraded into carbon dioxide and water in the presence of the photocatalyst. The results revealed that the easy-to-produce photocatalyst was stable and efficient in levofloxacin removing.

Exploring the binding mechanism and esterase-like activity of human serum albumin with levofloxacin and its choline based conjugates: A biophysical approach.

Human serum albumin (HSA) effectively binds to compounds having different molecular weight and thus facilitates their distribution in the living organisms. Thus, the binding interactions between a potential antibacterial drug (levofloxacin) and synthesized choline based levofloxacinate conjugates with HSA have been explored. The binding efficacy and mechanism were explored by utilizing different spectroscopic techniques; UV-Visible, steady state fluorescence, time resolved fluorescence and esterase-like activity. The interactions between the ligands and protein were electrostatic as well as hydrophobic in nature. The influence of different ligands having different alkyl chain shows quenching of the fluorescence emission of HSA. The spontaneous binding/quenching of HSA with ligands was static in nature, validated by steady state and time resolved fluorescence spectroscopy. Also, the impact of these ligands on the conformation of the native HSA structure was evaluated by using circular dichroism spectroscopy. In combination to the structural change study, the native protein functionality was observed (in terms of 'esterase-like activity') which has been found to be on lower side due to ligand binding. Further, we have performed the reverse study to check the impact of HSA on the fluorescent fluoroquinolone drug. The current study may prove helpful in elucidating the chemico-biological interactions which may prove useful in the pharmaceuticals, pharmacology, and different biochemistry fields.

Significance of non-DLVO interactions on the co-transport of levofloxacin and titanium dioxide nanoparticles in porous media.

With the application of engineered nanomaterials and antibiotics in the fields of medicine, aerospace, new energy and agriculture, the associated contamination is detected widely in soil-groundwater systems. It is of great scientific and practical significance to deeply explore the environmental interface process between nanoparticles and antibiotics for the scientific assessment of environmental fate and ecological environmental risks, as well as the development of new composite pollution control technologies. In this study, the co-transport behaviors of positively charged titanium dioxide nanoparticles (TiO2-NPs) and negatively charged levofloxacin (LEV) in quartz sand (QS) are investigated in this study. The results show that TiO2-NPs hardly flow out when transported alone in the column because of its positive charge, which creates a strong attraction with the negatively charged quartz sand on the surface. When TiO2-NPs co-migrate with LEV in porous media, the presence of LEV promotes the transport of TiO2-NPs, while the presence of TiO2-NPs inhibits LEV transport. Non-XDLVO interactions based on molecular dynamics (MD) simulations can help explain the observed promotion and inhibition phenomena as well as the correlation between TiO2-NPs and LEV. The results indicate that TiO2-LEV complexes or aggregates can be formed during the co-transportation process of TiO2-NPs and LEV in porous media. As flow velocity increases from 0.204 cm min-1 to 1.630 cm min-1, both the transport capacities of TiO2-NPs and LEV are enhanced significantly. Under the condition of high citric acid (CA) concentration (15 mmol L-1), the transport capacity of TiO2-NPs is slightly inhibited, while the transport capacity of LEV is enhanced. This study provides new insights into the transport of nanometallic oxides and antibiotics in porous media, which suggests that non-XDLVO interactions should be considered together when assessing the environmental risks and fate of nanometallic oxides and antibiotics in soil-groundwater systems.

Molybdenum disulphide nanoparticles accelerate the transformation of levofloxacin in planting soil upon exposure.

The use of nanocatalytic particles for the removal of refractory organics from wastewater is a rapidly growing area of environmental purification. However, little has been done to investigate the effects of nanoparticles on soil-plant systems with antibiotic contamination. This work assessed the effect of molybdenum disulfide (MoS2) on the soil-Phragmites communis system containing levofloxacin (LVX). The results showed that the addition of MoS2 had restoration potential for stressed plant. The MoS2 with catalytic activity promoted the transformation of LVX in rhizosphere soils. The transformation pathways of LVX in the different exposure groups were proposed. The continuous output of radicals in the high MoS2 dosage group facilitated the transformation of LVX to small molecule compounds, which were eventually mineralized. Moreover, the electron-density-difference analysis revealed the easier flow of electrons from the MoS2 surface towards the LVX molecules. This finding provides theoretical support for the application of nanocatalytic particles in ecological environments.

Photocatalytic degradation of antibiotics by N-doped carbon nanoflakes-nickel ferrite composite derived from algal biomass.

This work reports the synthesis of nickel ferrite (NiFe) nanoparticles, N-doped mesoporous carbon nanoflakes (NCF) and novel nickel ferrite-carbon nanoflakes (NiFe@NCF) nanocomposite using solvothermal method. NCF was derived from a cyanobacterial consortium consisting of Anabaena, Lyngbya and Weistiellopsis, rich in carbon and nitrogen. The synthesized nanoparticles were used as heterogeneous photocatalyst for degradation of two harmful water pollutants, ciprofloxacin (CIP) and levofloxacin (LEV). 99.91% LEV and 98.86% CIP were degraded within 50 and 70 min of visible light irradiation using NiFe@NCF following pseudo first order kinetics. This improved efficiency of the nanocomposite may be attributed to its higher surface area, reduction of band gap (from 2.42 to 2.19 eV), more active sites as well as charge carrier mobility with decreasing agglomeration tendency of the magnetic nickel nanoparticles upon being embedded on NCF. N-doping improves light harvesting property, retards charge recombination and extends as well as delocalises á´¨-conjugated system resulting in enhanced photocatalytic activity. The scavenging experiments and EPR analysis reveal that O2-• and •OH are the main active species taking part in the degradation process. The material performs well within a wide range of pH and can be effectively used up to 5 repetitive cycles. A feasible photocatalytic degradation mechanism of the antibiotics against NiFe@NCF nanocomposite is also put forwarded along with their possible degradation pathways from LCMS studies.

An antifouling supramolecular polymer ophthalmic ointment alleviates symblepharon in rat alkali burn eyes.

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.

ß-Cyclodextrin/carbon dots-grafted cellulose nanofibrils hydrogel for enhanced adsorption and fluorescence detection of levofloxacin.

In this study, a novel hydrogel, ß-cyclodextrin/carbon dots-grafted cellulose nanofibrils hydrogel (ßCCH), was fabricated for removal and fluorescence determination of levofloxacin (LEV). A comprehensive analysis was performed to characterize its physicochemical properties. Batch adsorption experiments were conducted, revealing that ßCCH reached a maximum adsorption capacity of 1376.9 mg/g, consistent with both Langmuir and pseudo-second-order models, suggesting that the adsorption process of LEV on ßCCH was primarily driven by chemical adsorption. The removal efficiency of ßCCH was 99.2 % under the fixed conditions (pH: 6, initial concentration: 20 mg/L, contact time: 300 min, temperature: 25 °C). The removal efficiency of ßCCH for LEV still achieved 97.3 % after five adsorption-desorption cycles. By using ßCCH as a fluorescent probe for LEV, a fast and sensitive method was established with linear ranges of 1-120 mg/L and 0.2-1.0 µg/L and a limit of detection (LOD) as low as 0.09 µg/L. The viability of ßCCH was estimated based on the economic analysis of the synthesis process and the removal of LEV, demonstrating that ßCCH was more cost-effective than commercial activated carbon. This study provides a novel approach for preparing a promising antibiotic detection and adsorption material with the advantages of stability, and cost-effectiveness.

Chitosan-coated liposome with lysozyme-responsive properties for on-demand release of levofloxacin.

As an anti-infection antibiotic delivery route, a drug-controlled release system based on a specific condition stimulus response can enhance drug stability and bioavailability, reduce antibiotic resistance, achieve on-demand release and improve targeting and utilization efficiency. In this study, chitosan-coated liposomes containing levofloxacin (Lef@Lip@CS) were prepared with lysozyme in body fluids serving as an intelligent "switch" to enable accurate delivery of antibiotics through the catalytic degradation ability of chitosan. Good liposome encapsulation efficacy (64.89 ± 1.86 %) and loading capacity (5.28 ± 0.18 %) were achieved. The controlled-release behavior and morphological characterization before and after enzymatic hydrolysis confirmed that the levofloxacin release rate depended on the lysozyme concentration and the degrees of deacetylation of chitosan. In vitro bacteriostatic experiments showed significant differences in the effects of Lef@Lip@CS before and after enzyme addition, with 6-h inhibition rate of 72.46 % and 100 %, and biofilm removal rates of 51 % and 71 %, respectively. These findings show that chitosan-coated liposomes are a feasible drug delivery system responsive to lysozyme stimulation.

Nanoparticle-hydrogel composite as dual-drug delivery system for the potential application of corneal graft rejection.

Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60 min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.

Inhalable solid lipid nanoparticles of levofloxacin for potential tuberculosis treatment.

Delivering novel antimycobacterial agents through the pulmonary route using nanoparticle-based systems shows promise for treating diseases like tuberculosis. However, creating dry powder inhaler (DPI) with suitable aerodynamic characteristics while preserving nanostructure integrity and maintaining bioactivity until the active ingredient travels deeply into the lungs is a difficult challenge. We developed DPI formulations containing levofloxacin-loaded solid lipid nanoparticles (SLNs) via spray-drying technique with tailored aerosolization characteristics for effective inhalation therapy. A range of biophysical techniques, including transmission electron microscopy, confocal microscopy, and scanning electron microscopy were used to measure the morphologies and sizes of the spray-dried microparticles that explored both the geometric and aerodynamic properties. Spray drying substantially reduced the particle sizes of the SLNs while preserving their nanostructural integrity and enhancing aerosol dispersion with efficient mucus penetration. Despite a slower uptake rate compared to plain SLNs, the polyethylene glycol modified formulations exhibited enhanced cellular uptake in both A549 and NR8383 cell lines. The percent viability of Mycobacterium bovis had dropped to nearly 0 % by day 5 for both types of SLNs. Interestingly, the levofloxacin-loaded SLNs demonstrated a lower minimum bactericidal concentration (0.25 µg/mL) compared with pure levofloxacin (1 µg/mL), which indicated the formulations have potential as effective treatments for tuberculosis.

Novel theranostic wounds dressing based on pH responsive alginate hydrogel/graphene oxide/levofloxacin modified silk.

Integrating pH sensor with controlled antibiotic release is fabricated on silk to create a theranostic wound dressing. Alginate (ALG) hydrogel and graphene oxide (GO) loaded with levofloxacin (LVX) and a pH indicator are applied to fabricate a pH-responsive theranostic wound dressing. The modified silk color changes from yellow to green in response to elevated skin pH, indicating the skin infection. The semi-quantitative analysis was conducted using ImageJ, revealing significant color changes across the wide range. At elevated pH levels, the ionization of the COOH bonds within ALG induces repulsion among the COO- groups, thereby accelerating the release of the incorporated drug compared to release under lower pH. At an infected pH of 8, ALG hydrogel triggers LVX releasing up to 135.86 ± 0.3 µg, while at a normal pH of 7, theranostic silk releases 123.13 ± 0.26 µg. Incorporating GO onto silk fibers enhances LVX loading and sustains LVX release. Furthermore, these modified silks possess antimicrobial abilities without causing irritation or allergies on the human skin. This theranostic silks represents a major step forward in smart wound care, introducing a versatile platform of smart wound care.