Plant-based green fabrication of CuO-CdO-bentonite S-scheme heterojunction with enhanced photocatalytic performance for the degradation of levofloxacin.

In this research, for the first time, CuO and CdO nanoparticles (NPs) were synthesized using Ferula persica and anchored on layered bentonite as a novel S-scheme nano-heterojunction (denoted as CuO-CdO-BT). Ferula persica acted as a naturally-sourced reducing agent and stabilizer for the synthesis of NPs. The performance of CuO-CdO-BT was evaluated for the degradation of levofloxacin from an aqueous solution under sunlight. The characterization results clarified that the bentonite as a support not only reduced the agglomeration of CuO and CdO NPs but also decreased the size of biosynthesized NPs, which increased the active surface of NPs and the photodegardation efficiency. The effect of operational reaction system variables was examined to optimize the photocatalytic capability of CuO-CdO-BT. Under optimum conditions (catalyst dosage = 0.4 g/L, LVF concentration = 10 mg/L and pH = 8), 96.11% of levofloxacin was degraded using CuO-CdO-BT after 30 min with degradation kinetic of 0.108 min-1, which was about 2.4 and 4.2 times higher than those of bare CuO and CdO NPs, respectively. The improvement of the photocatalytic degradation efficiency of CuO-CdO-BT compared to CuO and CdO NPs was due to preventing the recombination of charge carriers in the S-scheme system. The radical quenching experiments ascertained the generation of [Formula: see text]·OH, and [Formula: see text] species in the CuO-CdO-BT system, indicating that ·OH radicals have a more prominent role than [Formula: see text] and [Formula: see text] in the photocatalytic reaction. The six possible levofloxacin pathways of LVF degradation were suggested based on HPLC-MS analysis. Over 88.5% LVF was removed using CuO-CdO-BT after three catalyst reuse cycles, indicating a cost-effectiveness potential of the biosynthesized photocatalyst reusability. Almost complete mineralization of LVF was obtained by the CuO-CdO-BT photocatalyst after 180 min of reaction. Based on findings, the S-scheme mechanism of photo-generated electron-hole pairs transfer in the CuO-CdO-BT system was found. The unique structural features of the new generation of S-scheme heterojunction and green synthesis of NPs using plants provide promising photocatalysts to improve wastewater treatment.

Antimicrobial therapeutic enhancement of levofloxacin via conjugation to a cell-penetrating peptide: An efficient sonochemical catalytic process.

Herein, we make an effort to enhance the antimicrobial activity of levofloxacin (LVX) antibiotic via conjugation to a cell-penetrating peptide (CPP) including Cys-Gly-Ala-Phe-Pro-His-Arg. For this purpose, cysteine is used as a linker between the LVX and CPP chain, and two heterogeneous nanoscale catalytic systems are employed as the substantial alternatives for traditional peptide coupling reagents like N,N,N',N'-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (TBTU). Briefly, it has been found out that the antimicrobial potency of the synthesized CPP-LVX conjugate (on the gram-positive and gram-negative bacteria) is noticeably enhanced (~20% more). It has been revealed via zone of inhibition (ZOI) and optical density (OD) evaluations. As a convenient method for making this type of the effective conjugations, ultrasound waves (with a specific frequency and power density) activate the catalytic sites of the heterogeneous nanoparticles. Through this synergistic effect, peptide/amide bond is formed during a short time (10 min), and high reaction yield (>90%) is obtained under mild conditions. Moreover, as a simple purification process, the catalyst nanoparticles are collected and separated through their high magnetic property.

Tailored Nanocarriers for the Pulmonary Delivery of Levofloxacin against Pseudomonas aeruginosa: A Comparative Study.

Cystic fibrosis (CF) patients are faced with chronic bacterial infections displaying persistent resistance if not eradicated during the first stage of the disease. Nanoantibiotics for pulmonary administration, such as liposomal ciprofloxacin or amikacin, have progressed through clinics thanks to their sustained release, prolonged lung residence time, and low systemic absorption. In this work, we sought a nanoformulation of levofloxacin for the treatment of Pseudomonas aeruginosa. We prepared and compared poly(lactic acid)-grafted-poly(ethylene glycol) nanoparticles, as well as anionic and cationic liposomes for their size, charge, and encapsulation efficiency. Cationic liposomes were unable to encapsulate any drug and were subsequently considered as a control formulation. Regarding the efficiency of the nanocarrier, anionic liposomes exhibited a prolonged release over 72 h and preserved the antibacterial activity of levofloxacin against five strains of P. aeruginosa, whereas polymeric nanoparticles quickly released their entire payload and increased the minimum inhibitory concentration of levofloxacin. Thus, only anionic liposomes were considered for further preclinical development. Anionic liposomes exhibited a suitable colloidal stability in Turbiscan analysis and crossed a layer of artificial mucus in under 1 h in a Transwell setup. Despite their negative surface charge, liposomes still interacted with the P. aeruginosa membrane in a dose-response manner, as demonstrated by flow cytometry. Viability assays confirmed that anionic liposomes, loaded or not, exhibited a good safety profile on A549 epithelial cells, even at high concentrations. Finally, nebulization of anionic liposomes containing levofloxacin did not impact their colloidal stability, and the droplet size distribution was suitable for deep lung deposition, where the P. aeruginosa infection lies. Therefore, levofloxacin-loaded anionic liposomes exhibited suitable properties for the pulmonary treatment of P. aeruginosa in CF. This step-by-step study confirms the promising role of liposomes for lung administration of antibiotics, as recently seen in clinics, and fosters their development for several types of antibiotics.

Application of Deep Eutectic Solvents in Hybrid Molecularly Imprinted Polymers and Mesoporous Siliceous Material for Solid-Phase Extraction of Levofloxacin from Green Bean Extract.

Deep eutectic solvents (DES) are potential ecofriendly surfactants for the preparation of materials. In this study, both molecularly imprinted polymers (MIPs) and mesoporous siliceous materials (MSMs) were modified by betaine-based DES. Six materials were employed as solid phase extraction (SPE) adsorbents for the rapid purification of levofloxacin. The DES-based materials showed better selective adsorption than the conventional materials. The adsorption curves of DES-MIP showed superior molecular recognition ability and binding capability for levofloxacin compared to the other materials. The limit of detection and limit of quantitation of the method were 0.01 and 0.03 µg/mL for levofloxacin, respectively. The method recoveries at three spiked levels were 97.2 - 100.2% for DES-MIP, with an RSD <1.8%. DES-MIP showed the highest selective recovery (95.2%) for levofloxacin from the green bean extract, and could remove the interferent effectively.

Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients.

OBJECTIVE: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis. METHODS: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI). RESULTS: After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro-homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5 µm; however, levofloxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations. CONCLUSION: Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.

Encapsulation of Antibiotic Levofloxacin in Biocompatible Microemulsion Formulation: Insights from Microstructure Analysis.

Microemulsions (µEs) are unique systems that offer exciting perspectives in biophysical research for mimicing biomembranes at the molecular level. In the present study, biocompatible µE formulation of a new oil-in-water (o/w) system comprising clove oil/Tween 20/2-propanol/water was accomplished for encapsulating an antibiotic, levofloxacin (LVF). The pseudoternary phase diagram was delineated at a constant cosurfactant/surfactant (2:1) ratio to meet the economic feasibility. The gradual changes occurring in the microstructure of the as-formulated four-component µEs were explored via multiple complementary characterization techniques. The results of electrical conductivity (σ), viscosity (η), and optical microscopic measurements suggested the existence of a percolation transition to a bicontinuous structure in the microregions of the as-formulated µE. LVF displayed a high solubility (5.0 wt %) at the pH of 6.9 in an optimum µE formulation comprising 2-propanol (36.4%), Tween 20 (18.2%), clove oil (20.7%), and water (24.7%). The LVF-loaded µE composition showed long-term stability for over 6 months of storage. Fourier transform IR analysis showed that LVF was stable inside the µE formulation, indicating the absence of any possible aggregation of LVF. Dynamic light scattering revealed that the average particle size of drug-free µE (64.5 ± 3.4 nm) increases to 129.7 ± 5.8 nm upon loading of LVF, suggesting the accumulation of LVF in the interfacial layers of the micelles. Moreover, fluorescence measurements indicated that LVF might be localized in the interfacial film of µE system, which may result in a controlled release of drug.

Pleiotropic Effects of Levofloxacin, Fluoroquinolone Antibiotics, against Influenza Virus-Induced Lung Injury.

Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-γ in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs.

Levofloxacin and indolicidin for combination antimicrobial therapy.

Despite the increasing need for antibiotics to fight infectious diseases, fewer new antibiotics are available on the market. Unfortunately, developing a new class of antibiotics is associated with high commercial risk. Therefore, modification or combination of existing antibiotics to improve their efficacy is a promising strategy. Herein, we conjugated the antibiotic, levofloxacin, with two peptides, i.e. an antimicrobial peptide indolicidin and a cell penetrating peptide (TAT). Glycolic acid and glycine linkers were used between levofloxacin and peptides. We developed an optimized condition for coupling of levofloxacin via its carboxylic group to glycolic acid using solid phase peptide synthesis (SPPS). Antibacterial and haemolytic assays were carried out on the conjugates and only the levofloxacin-indolicidin conjugate demonstrated moderate antibacterial activity. Interestingly, physical mixture of levofloxacin and indolicidin showed improvement in the activity against Gram-positive bacteria.

Formulation and in vitro evaluation of size expanding gastro-retentive systems of levofloxacin hemihydrate.

Size increasing (plug-type) levofloxacin hemihydrate (LVF) tablets for eradication of Helicobacter pylori (H. pylori) were prepared using in situ gel forming polymers including: gellan gum, sodium alginate, pectin and xanthan gum. Effect of cross-linkers: calcium and aluminum chloride, on the drug release was also studied. The prepared tablets were evaluated for their physicochemical parameters: weight variation, thickness, friability, hardness, drug content, water uptake and in vitro drug release. The optimized formula was subjected to further studies such as radial swelling test, FT-IR and DSC. Results revealed that LVF release depends not only on the nature of the matrix but also on the type of cross linker used to form this polymeric matrix. The addition of either calcium chloride or aluminum chloride, as cross-linkers, to gellan gum formulations significantly decreased drug release. Other polymers' formulations resulted in increased drug release upon addition of the same cross-linkers. The formula containing xanthan gum without any cross linker showed the most sustained LVF release with an increase in diameter with time, thus acting as a plug-type dosage form. IR spectra and DSC thermograms of LVF, xanthan gum, and a physical mixture of both, indicated that there was no interaction between the drug and the polymer and confirmed the drug stability.