Moringa concanensis-Mediated Synthesis and Characterizations of Ciprofloxacin Encapsulated into Ag/TiO2/Fe2O3/CS Nanocomposite: A Therapeutic Solution against Multidrug Resistant E. coli Strains of Livestock Infectious Diseases.

Background: Multidrug resistant MDR bacterial strains are causing fatal infections, such as mastitis. Thus, there is a need for the development of new target-oriented antimicrobials. Nanomaterials have many advantages over traditional antibiotics, including improved stability, controlled antibiotic release, targeted administration, enhanced bioavailability, and the use of antibiotic-loaded nanomaterials, such as the one herein reported for the first time, appear to be a promising strategy to combat antibiotic-resistant bacteria. The use of rationally designed metallic nanocomposites, rather than the use of single metallic nanoparticles (NPs), should further minimize the bacterial resistance. Aim: Green synthesis of a multimetallic/ternary nanocomposite formed of silver (Ag), titanium dioxide (TiO2), and iron(III) oxide (Fe2O3), conjugated to chitosan (CS), in which the large spectrum fluoroquinolone antibiotic ciprofloxacin (CIP) has been encapsulated. Methods: The metallic nanoparticles (NPs) Ag NPs, TiO2 NPs, and Fe2O3 NPs were synthesized by reduction of Moringa concanensis leaf aqueous extract. The ternary junction was obtained by wet chemical impregnation technique. CIP was encapsulated into the ternary nanocomposite Ag/TiO2/Fe2O3, followed by chitosan (CS) conjugation using the ionic gelation method. The resulting CS-based nanoparticulate drug delivery system (NDDS), i.e., CIP-Ag/TiO2/Fe2O3/CS, was characterized in vitro by gold standard physical techniques such as X-ray diffractometry (XRD), field emission scanning electron microscopy (FESEM), Fourier-transform infrared (FTIR) spectroscopy. Pharmacological analyses (i.e., LC, EE, ex-vivo drug release behavior) were also assessed. Further, biological studies were carried out both ex vivo (i.e., by disk diffusion method (DDM), fluorescence-activated single cell sorting (FACS), MTT assay) and in vivo (i.e., antibacterial activity in a rabbit model, colony-forming unit (CFU) on blood agar, histopathological analysis using H&E staining). Results: The encapsulation efficiency (EE) and the loading capacity (LC) of the NDDS were as high as 94% ± 1.26 and 57% ± 3.5, respectively. XRD analysis confirmed the crystalline nature of the prepared formulation. FESEM revealed nanorods with an average diameter of 50−70 ± 12 nm. FTIR confirmed the Fe-O-Ti-CS linkages as well as the successful encapsulation of CIP into the NDDS. The zeta potential (ZP) of the NDDS was determined as 85.26 ± 0.12 mV. The antimicrobial potential of the NDDS was elicited by prominent ZIs against MDR E. coli (33 ± 1.40 mm) at the low MIC of 0.112 µg/mL. Morphological alterations (e.g., deformed shape and structural damages) of MDR pathogens were clearly visible overtime by FESEM after treatment with the NDDS at MIC value, which led to the cytolysis ultimately. FACS analysis confirmed late apoptotic of the MDR E. coli (80.85%) after 6 h incubation of the NDDS at MIC (p < 0.05 compared to untreated MDR E. coli used as negative control). The highest drug release (89% ± 0.57) was observed after 8 h using PBS medium at pH 7.4. The viability of bovine mammary gland epithelial cells (BMGE) treated with the NDDS remained superior to 90%, indicating a negligible cytotoxicity (p < 0.05). In the rabbit model, in which infection was caused by injecting MDR E. coli intraperitoneally (IP), no colonies were detected after 72 h of treatment. Importantly, the histopathological analysis showed no changes in the vital rabbit organs in the treated group compared to the untreated group. Conclusions: Taken together, the newly prepared CIP-Ag/TiO2/Fe2O3/CS nanoformulation appears safe, biocompatible, and therapeutically active to fight MDR E. coli strains-causing mastitis.

Synthesis and Characterization of Carbon Dots Coated CaCO3 Nanocarrier for Levofloxacin Against Multidrug Resistance Extended-Spectrum Beta-Lactamase Escherichia coli of Urinary Tract Infection Origin.

The multidrug resistance (MDR) Escherichia coli having Extended-Spectrum Beta-Lactamase (ESBL) genes and the capacity to create a biofilm acts as a major reduction in the therapeutic effectiveness of antimicrobials. In search of a novel nanocarrier (NC) for targeted delivery of antibiotics, carbon dots (CDs) coated calcium carbonate nanocarriers (CCNC) from organic chicken eggshells conjugated with levofloxacin (Lvx) were synthesized. Our main objectives were to explore the antimicrobial, antibiofilm, and NC potential of CDs coated CaCO3 Nanocarrier conjugated with levofloxacin (CD-CCNC-Lvx) to combat biofilm-producing MDR ESBL E. coli of urinary tract infection origin. The synthesized NC system was physiochemically characterized, validating the synthesis of CCNC and CD-CCNC-Lvx with a particle size of 56 and 14 nm, respectively. Scanning electron microscopy (SEM) showed rod shape morphology. X-ray diffraction results discovered crystalline and dispersed nanoparticles. In vitro release drug kinetics illustrated sustained release of Lvx. NC system exhibited strong antibacterial and antibiofilm potential against E. coli with a noticeable low minimal inhibitory concentration (MIC). MIC of CCNC was found to be 30 ± 0.1 µg/mL and CD-CCNC-Lvx was 20 ± 0.1 µg/mL for MDR ESBL-producing E. coli. The synergistic effect of NC upon conjugation with Lvx showed incredible activity with 30 mm zone of inhibition and 68% biofilm inhibition. Flow cytometry analysis revealed treated E. coli cells showed 58.69% reduction in cell viability. SEM images of treated bacterial cells showed morphological changes, which were also confirmed by our flow cytometry findings leading to cell membrane damage in E. coli. NC system also downregulated the blaCTX-M gene in E. coli. The hemolytic analysis proved biocompatibility with human red blood cells (RBCs). It is concluded that CCNC has the potential to be used as NC for target delivery of antibiotics and may combat toxicity of antibiotics as the inhibition of E. coli was noticed at low MIC concentration.

Competitive role of nitrogen functionalities of N doped GO and sensitizing effect of Bi2O3 QDs on TiO2 for water remediation.

The promising solar irradiated photocatalyst by pairing of bismuth oxide quantum dots (BQDs) doped TiO2 with nitrogen doped graphene oxide (NGO) nanocomposite (NGO/BQDs-TiO2) was fabricated. It was used for degradation of organic pollutants like 2,4-dichlorophenol (2,4-DCP) and stable dyes, i.e. Rhodamine B and Congo Red. X-ray diffraction (XRD) profile of NGO showed reduction in oxygenic functional groups and restoring of graphitic crystal structure. The characteristic diffraction peaks of TiO2 and its composites showed crystalline anatase TiO2. Morphological images represent spherical shaped TiO2 evenly covered with BQDs spread on NGO sheet. The surface linkages of NO-O-Ti, C-O-Ti, Bi-O-Ti and vibrational modes are observed by Fourier transform infrared spectroscopy (FTIR) and Raman studies. BQDs and NGO modified TiO2 results into red shifting in visible region as studied in diffused reflectance spectroscopy (DRS). NGO and BQDs in TiO2 are linked with defect centers which reduced the recombination of free charge carriers by quenching of photoluminescence (PL) intensities. X-ray photoelectron spectroscopy (XPS) shows that no peak related to C-O in NGO/BQDs-TiO2 is observed. This indicated that doping of nitrogen into GO has reduced some oxygen functional groups. Nitrogen functionalities in NGO and photosensitizing effect of BQDs in ternary composite have improved photocatalytic activity against organic pollutants. Intermediate byproducts during photo degradation process of 2,4-DCP were studied through high performance liquid chromatography (HPLC). Study of radical scavengers indicated that O2·- has significant role for degradation of 2,4-DCP. Our investigations propose that fabricated nanohybrid architecture has potential for degradation of environmental pollutions.

Breast Cancer Inhibition by Biosynthesized Titanium Dioxide Nanoparticles Is Comparable to Free Doxorubicin but Appeared Safer in BALB/c Mice.

Cancer remains a global health burden prompting affordable, target-oriented, and safe chemotherapeutic agents to reduce its incidence rate worldwide. In this study, a rapid, cost-effective, and green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) has been carried out; Ex vivo and in vivoevaluation of their safety and anti-tumor efficacy compared to doxorubicin (DOX), a highly efficient breast anti-cancer agent but limited by severe cardiotoxicity in many patients.Thereby,TiO2 NPs were eco-friendly synthetized using aqueous leaf extract of the tropical medicinal shrub Zanthoxylum armatum as a reducing agent. Butanol was used as a unique template. TiO2 NPs were physically characterized by ultraviolet-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) as routine state-of-the art techniques. The synthesized TiO2 NPs were then evaluated for their cytotoxicity (by MTT, FACS, and oxidative stress assays) in 4T1 breast tumor cells, and their hemocompatibility (by hemolysis assay). In vivo anti-tumor efficacy and safety of the TiO2 NPs were further assessed using subcutaneous 4T1 breast BALB/c mouse tumor model.The greenly prepared TiO2 NPs were small, spherical, and crystalline in nature. Interestingly, they were hemocompatible and elicited a strong DOX-like concentration-dependent cytotoxicity-induced apoptosis both ex vivo and in vivo (with a noticeable tumor volume reduction). The underlying molecular mechanism was, at least partially, mediated through reactive oxygen species (ROS) generation (lipid peroxidation). Unlike DOX (P < 0.05), it is important to mention that no cardiotoxicity or altered body weight were observed in both the TiO2 NPs-treated tumor-bearing mouse group and the PBS-treated mouse group (P > 0.05). Taken together, Z. armatum-derived TiO2 NPs are cost-effective, more efficient, and safer than DOX. The present findings shall prompt clinical trials using green TiO2 NPs, at least as a possible alternative modality to DOX for effective breast cancer therapy.

Bursting the Virulence Traits of MDR Strain of Candida albicans Using Sodium Alginate-based Microspheres Containing Nystatin-loaded MgO/CuO Nanocomposites.

INTRODUCTION: Candida albicans is a major opportunistic pathogen that causes a wide range of human infections. Currently available therapeutic agents are limited for treating these fungal infections due to multidrug resistance as well as their nonbiodegradability, poor biocompatibility and toxicity. In order to battle these limitations, we have synthesized a polymeric system as microcarriers to deliver the antifungal drug. The objective of the present study was to immobilize MgO/CuO nanocomposite and nystatin-loaded MgO/CuO nanocomposites in nontoxic, nonimmunogenic, biodegradable and biocompatible sodium alginate microspheres for the first time. MATERIALS AND METHODS: Nanoparticle-loaded sodium alginate microspheres were prepared by ionotropic gelation technique using calcium chloride as a cross-linker. Synthesized microspheres were characterized using standard characterization techniques and were evaluated for biological activity against MDR strain of C. albicans. RESULTS: Characterization of microspheres by Fourier-transform infrared spectroscopy confirmed loading of Nys-MgO/CuO NPs, scanning electron microscopy (SEM) revealed rough spherical beads with a highly porous surface having an average size in the range of 8-10 µm. X-ray diffraction (XRD) analyzed its semicrystalline structure. Entrapment efficiency of Nys-MgO/CuO NPs was 80% and release kinetic study revealed sustained and prolonged release of drug in pH 5.5. Flow cytometry analysis showed yeast cell death caused by Nys-MgO/CuO MS exhibits late apoptotic features. In cytotoxicity assay 5-14 mg of microspheres did not cause hemolysis. Microspheres reduced virulence traits of C. albicans such as germ tube and biofilm formation were compromised at concentration of 5 mg/mL. Antimicrobial assessment results revealed a pronounced inhibitory effect against C. albicans. CONCLUSION: The in vitro experiments have shown promising results based on good stability, Nys-MgO/CuO NP-encapsulated microspheres can be used as a prolonged controlled release system against MDR pathogenic C. albicans.

Targeting microbial biofilms: by Arctium lappa l. synthesised biocompatible CeO2-NPs encapsulated in nano-chitosan.

This study is planned to synthesise new biocompatible, nano antimicrobial formulation against biofilm producing strains. Aqueous root extract of Arctium lappa l. was used to synthesise ceria nanoparticles (CeO2-NPs). The synthesised nanoparticles were encapsulated with nano-chitosan by sol-gel method and characterised using standard techniques. Gas chromatography-mass spectrometer of Arctium lappa l. revealed the presence of ethanol, acetone, 1- propanol, 2-methylethane, 1,1-di-ethoxy, 1-Butanol, and oleic acid acted as reducing and surface stabilising agents for tailoring morphology of CeO2-NPs. Erythrocyte integrity after treatment with synthesised nanomaterials was evaluated by spectrophotometer measurement of haemoglobin release having biocompatibility. Scanning electron microscopy revealed the formation of mono dispersed beads shaped particles with mean particle size of 26.2 nm. X-ray diffractometry revealed cubic crystalline structure having size of 28.0 nm. After encapsulation by nano-chitosan, the size of CeO2-NPs enhances to 48.8 nm making average coverage of about 22.6 nm. The synthesised nanomaterials were found effective to disrupt biofilm of S. aureus and P. aeruginosa. Interestingly, encapsulated CeO2-NPs revealed powerful antibacterial and biofilm disruption activity examined by fluorescent live/dead staining using confocal laser scanning microscopy. The superior antibacterial activities exposed by encapsulated CeO2-NPs lead to the conclusion that they could be useful for controlling biofilm producing multidrug resistance pathogens.

Nitrogen doped carbon quantum dots and GO modified WO3 nanosheets combination as an effective visible photo catalyst.

Nitrogen doped carbon quantum dots (NCQDs) based highly efficient ternary photocatalyst are fabricated by modifying surface of GO incorporated WO3 nano-sheets. XRD confirmed the formation of monoclinicWO3 nano-sheets. All the characteristic peaks of WO3, GO and NCQDs are obvious in XRD patterns of WO3/GO/NCQDs ternary photocatalysts confirming successful fabrication of the photocatalysts. SEM images showed that WO3 host matrix is distorted after incorporation of GO and NCQDs owing to lower interfacial tension. The surface of WO3 nano-sheets is modified with morphological defects making more active sites available. UV-vis spectra exhibited extended visible light absorption and remarkable reduction of WO3 band gap energy. The photoluminescence spectra confirmed the efficient charge separation in NCQDs modified ternary photocatalyst. The synthesized composites were applied for the photocatalytic degradation of harmful organic dye i.e. methyl orange (MO). The ternary composites represented the excellent photocatalytic activity as compared to binary and pure WO3 photocatalysts. This enhanced photocatalytic activity is attributed to the availability of active sites, extended light absorption in visible region and enhanced charge separation efficiency.

Synergistic evaluation of AgO2 nanoparticles with ceftriaxone against CTXM and blaSHV genes positive ESBL producing clinical strains of Uro-pathogenic E. coli.

The silver oxide nanoparticles (AgO2-NPs) were synthesised using silver foil as a new precursor in wet chemical method. X-ray diffraction analysis shows crystallographic structures of AgO2-NPs with crystallite size of 35.54 nm well-matched with standard cubic structure. Scanning electron microscopy analysis clearly shows the random distribution of spherical-shaped nanoparticles. Energy dispersive X-ray analysis confirmed the purity of the samples as it shows no impurity element. Fourier transforms infra-red analysis confirmed the formation of AgO2-NPs with the presence of Ag-O-Ag stretching bond. All the techniques also confirmed the loading of ceftriaxone drug on the surface of AgO2-NPs. This study also described the effect of AgO2-NPs having synergistic activity with ß lactam antibiotic i.e. ceftriaxone against ESBL generating Escherichia coli (E. coli). Among isolated strains of E. coli, 60.0% were found to be ESBL producer. The synergistic activities of AgO2-NPs with ceftriaxone suggest that these combinations are effective against MDR-ESBL E. coli strains as evident by increase in zone sizes. The present study observed rise in MDR-ESBL E. coli with polymorphism of blaCTXM and blaSHV causing UTI infections in Pakistani population. The antibiotic and AgO2-NPs synergistic effect can be used as an efficient approach to combat uro-pathogenic infections.

Study of Graphene Oxide Structural Features for Catalytic, Antibacterial, Gas Sensing, and Metals Decontamination Environmental Applications.

This study represents a comprehensive review about the structural features of graphene oxide (GO) and its significance in environmental applications. Two dimensional (2D) GO is tremendously focused in advanced carbon-based nanomaterials for environmental applications due to its tunable physicochemical characteristics. Herein, we report foundational structural models of GO and explore the chemical bonding of oxygen moieties, with graphite basal plane using various characterization tools. Moreover, the impact of these oxygen moieties and the morphology of GO for environmental applications such as removal of metal ions and catalytic, antibacterial, and gas sensing abilities have here been critically reviewed for the first time. Environmental applications of GO are highly significant because, in the recent era, the fast progress of industries, even in the countryside, results in air and water pollution. GO has been widely investigated by researchers to eradicate such environmental issues and for potential industrial and clinical applications due to its 2D structural features, large surface area, presence of oxygen moieties, nonconductive nature, intense mechanical strength, excellent water dispersibility, and tunable optoelectronic properties. Thence, particular emphasis is directed toward the modification of GO by varying the number of its oxygen functional groups and by coupling it with other exotic nanomaterials to induce unique properties in GO for potential environmental remediation purposes.

Biosynthesis and characterisation of nano-silica as potential system for carrying streptomycin at nano-scale drug delivery.

A growing trend within nanomedicine has been the fabrication of self-delivering supramolecular nanomedicines containing a high and fixed drug content ensuring eco-friendly conditions. This study reports on green synthesis of silica nanoparticles (Si-NPs) using Azadirachta indica leaves extract as an effective chelating agent. X-ray diffraction analysis and Fourier transform-infra-red spectroscopic examination were studied. Scanning electron microscopy analysis revealed that the average size of particles formed via plant extract as reducing agent without any surfactant is in the range of 100-170 nm while addition of cetyltrimethyl ammonium bromide were more uniform with 200 nm in size. Streptomycin as model drug was successfully loaded to green synthesised Si-NPs, sustain release of the drug from this conjugate unit were examined. Prolong release pattern of the adsorbed drug ensure that Si-NPs have great potential in nano-drug delivery keeping the environment preferably biocompatible, future cytotoxic studies in this connection is helpful in achieving safe mode for nano-drug delivery.

Bismuth-doped ordered mesoporous TiO2: visible-light catalyst for simultaneous degradation of phenol and chromium.

A controllable and reproducible synthesis of highly ordered two-dimensional hexagonal mesoporous, crystalline bismuth-doped TiO(2) nanocomposites with variable Bi ratios is reported here. Analyses by transmission electron microscopy, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy reveal that the well-ordered mesostructure is doped with Bi, which exists as Bi(3+) and Bi((3+x+)). The Bi-doped mesoporous TiO(2) (ms-TiO(2)) samples exhibit improved photocatalytic activities for simultaneous phenol oxidation and chromium reduction in aqueous suspension under visible and UV light over the pure ms-TiO(2), P-25, and conventional Bi-doped titania. The high catalytic activity is due to both the unique structural characteristics and the Bi doping. This new material extends the spectral response from UV to the visible region, and reduces electron-hole recombination, which renders the 2.0% Bi-doped ms-TiO(2) photocatalyst highly responsive to visible light.