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N-Acetylcysteine (NAC) loaded PLGA nanoparticles were prepared by electrospray method. The influence of independent parameters such as concentration, flow rate and nozzle to collector distance was studied on particle size and size distribution of generated nanoparticles using a Box–Behnken experimental design. Smallest size was found to be obtained at minimum value for both flow rate and concentration of polymer, regardless of collecting distance value in the ranges studied. Additionally, the minimum value of size distribution was observed at lowest values of both concentration of polymer and collecting distance, regardless of flow rate value. In total, a sample with minimum size and polydispersity was predicted to have flow rate, polymer concentration and collecting distance values of 0.06 (ml/h), 0.5 (%w/w) and 9.28 (cm), respectively. The experimentally prepared nanoparticles with lowest size and size distribution values, had a size of 122 (nm) and size distribution of 24. Zeta potential, drug loading and encapsulation efficiency of optimized nanoparticles were −6.58, 5% and 54.5%, respectively.

Magnetically separable nanospheres consisting of polyethyleneimine (PEI) and succinated PEI grafted on silica coated magnetite (Fe3O4) were prepared and characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, vibrating sample magnetometer, scanning electron microscopy and transmission electron microscopy. The prepared magnetic nanoparticles were then applied for physical adsorption or covalent attachment of Thermomyces lanuginosa lipase (TLL) via glutaraldehyde or hexamethylene diisocyanate. The reusability, storage, pH and thermal stabilities of the immobilized enzymes compared to that of free lipase were examined. The obtained results showed that the immobilized lipase on MNPs@PEI-GLU was the best biocatalyst which retained 80% of its initial activity after 12 cycles of application. The immobilized lipase on the selected support (MNPs@PEI-GLU) was also applied for the synthesis of ethyl valerate. Following 24 h incubation of the immobilized lipase on the selected support in n-hexane and solvent free media, the esterification percentages were 72.9% and 28.9%, respectively.

This study assessed the immobilization of laccase on CPC silica beads and removal of two sulfonamides, sulfathiazole (STZ) and sulfamethoxazole (SMZ), using free and immobilized laccase. The results showed that free laccase (1 U ml −1 ) removed 66% and 77% of SMZ and STZ, respectively, in the presence of 1-hydroxybenzotriazole (1 mM) as a laccase mediator after incubation at 40 °C for 1 h. Maximum enzymatic removal of both applied sulfonamides was achieved at a temperature of 50 °C and a pH of 5. At the elevated temperature of 70 °C, immobilized laccase removed 71.7% of STZ and 53% of SMZ. After ten cycles of removal experiments, 63.3% and 82.6% of the initial activity of the immobilized laccase toward SMZ and STZ remained, respectively. A lower K m value for STZ (0.056 mM) compared to that of SMZ (0.096 mM) confirmed a higher affinity of immobilized laccase toward STZ. A microtoxicity study of the inhibition of bacterial growth showed a decrease in toxicity of the laccase-treated sulfonamide solution.

A novel series of dihydropyrano[3,2-c]quinoline derivatives 6a–q were synthesized and evaluated for their in vitro α-glucosidase inhibitory activities. All newly synthesized compounds displayed potent α-glucosidase inhibitory activity in the range of 10.3 ± 0.3 µM–172.5 ± 0.8 µM against the yeast α-glucosidase enzyme when compared to the standard drug acarbose (IC50 = 750.0 ± 1.5 µM). Among these compounds, compounds 6e and 6d displayed the most potent α-glucosidase inhibitory activity (IC50 = 10.3 ± 0.3 and 15.7 ± 0.5 µM, respectively). The kinetic analysis of the most potent compounds 6e and 6d revealed that compound 6e inhibited α-glucosidase in an uncompetitive manner (Ki = 11 µM) while compound 6d was a non-competitive inhibitor (Ki = 28 µM) of the enzyme. Then, the cytotoxicity of the most potent compounds (i.e., compounds 6a, 6d, 6e, 6 g, 6j, and 6l) were evaluated for toxicity using the breast cancer cell lines MDA-MB231, MCF-7, and T-47D by using a MTT assay, and no toxicity was observed.

Lignocellulose is considered a major source for the production of valuable chemicals. Efficient degradation of lignin as the natural carrier of the lignocellulosic biomass represents a key limiting factor in biomass digestibility. Recently, biological delignification methods have been promoted as sustainable and environmentally friendly alternatives to the traditional technologies. In this study, porous nanocomposite of Fe

Tyrosine kinase inhibitors (TKIs) are blockers of tyrosine kinase proteins which are known for the activation of signaling pathways especially in neoplastic cells. TKIs are among targeted anticancer medications that are available in the market. Imatinib was introduced in the late 1990s as the first TKI medicine in oncology, followed by gefitinib, erlotinib, sorafenib, sunitinib, dasatanib and the list of TKIs is being updated nearly every month. To review the safety, efficacy, and current clinical stage of TKIs in different malignancies, particularly leukemia, advanced gastrointestinal and breast cancer, whole literature over the last decade (2006 to 2017) were searched to find all related studies. Criticizing current data indicates that TKIs have shown better clinical outcome in terms of both safety and efficacy compared to conventional therapies. Meanwhile, regarding the results of available clinical trials, the best approach into maximizing the benefits of this novel targeting therapy and also minimizing the undesirable adverse effects, is to evaluate the pharmacogenetic data of patients before allocating these agents in their treatment setting.

Extremozymes have gained importance for their ability to efficiently develop the processes in rigorous industrial conditions with incidence in the recycling of especially robust natural wastes. The production of an extracellular laccase from the halophilic bacterium Chromohalobacter salexigens aided for the bio-delignification of almond shell was optimized using response surface methodology followed by one-factor-at-a-time, resulting in an 80-fold increase in the enzyme yield. Out of 10 different medium components, CuSO4, ZnSO4, glucose, and urea were shown to have the greatest effects on the laccase production. The crude laccase was surprisingly stable against the various solvents, salts, chemicals, pH ranges, and temperatures, and it exhibited a high catalytic efficiency to a wide range of phenolic and non-phenolic substrates. Laccase reduced the kappa number of the lignin of almond shell by approximately 27% without the aid of a mediator, and the delignification efficiency strengthened by up to 58% reduction in kappa number in the used harsh conditions. Due to the high potential of the enzyme in delignification, specifically under extreme conditions, laccase from C. salexigens can be considered as an ideal alternative for chemical treatment methods in cellulose fibres extraction of lignocellulosic bio-wastes or delignification of the lignin and lignin-derived industrial wastes.

BACKGROUND Fabrication of nanocomposites with a magnetic core and their applications for enzyme immobilization has been introduced as an intresting trend during recent decades. The present study described the synthesis of polyethyleneimine (PEI) and β-cyclodextrin grafted PEI nanocomposites with magnetic cores and their applications for lipase immobilization. Fe3O4 magnetic nanoparticles (MNPs) were prepared by co-precipitation of Fe (III) and Fe (II) ions and then coated with polyethylenimine and/or hydroxyapatite/polyethylenimine, followed by grafting β-cyclodextrin onto the surface of the prepared nanocomposites. The nanocomposites were then characterized using Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, vibrating sample magnetometry, and scanning and transmission electron microscopy and consequently applied for the immobilization of lipase. RESULTS The results obtained for thermal and pH stability, reusability, and storage stability showed that the MNPs@hydroxyapatite/polyethylenimine/β-cyclodextrin was the best nanocomposite for lipase immobilization. Application of the immobilized lipase onto the selected nanocomposite for the synthesis of ethyl valerate (green apple flavor) revealed esterification rates of 79% and 62% in n-hexane and dimethyl sulfoxide, respectively, after 24 h incubation. CONCLUSION The results obtained demonstrate good stability, reusability, and potential application of immobilized lipase on magnetic nanocomposite of MNPs@hydroxyapatite/polyethylenimine/β-cyclodextrin for synthesis of ethyl valerate especially in organic medium. © 2014 Society of Chemical Industry

Application of subcritical and supercritical water technology for destruction of pharmaceutical compounds (carbamazepine, metoprolol and sulfamethaxazole) was investigated. The experiments were conducted inside batch reactor at a temperature ranging from 473 to 773 K and with different residence times of 5 to 50 min. The results show that carbamazepine, metoprolol and sulfamethaxazole are destructed by 90.27%, 99.99% and 98.84% after a 20 min exposure to 623 K, 673 K and 573 K, respectively. In comparison with the conventional methods of pharmaceutical waste treatment, the current technology provides a higher destruction efficiency (approximately 90–100%) which is achievable in shorter durations. NaOH and CuSO 4 ·5H 2 O were also applied as catalysts in the temperature range of 473 K to 723 K. Comparing these catalysts, CuSO 4 ·5H 2 O demonstrates a higher destruction efficiency, especially at lower temperatures. Based on the proposed pathway, the products of destructioncan be classified as environmentally-friendly compounds. The results show that this technology can be used as a green alternative for efficient removal of pharmaceutical compounds from wastewater streams.

Many retinal specialists have utilized intravitreal bevacizumab as an anti-VEGF to treat choroidal neovascularization (CNV), secondary to age-related macular degeneration (AMD) and pathological myopia, with favorable results. Bevacizumab is currently approved only for the systemic treatment of colon carcinoma, whereas it is widely used off-label for treating ocular neovascular diseases.In this review, after thorough search, 33 relevant studies conducted in the last 4 years were found. These articles comprised 14 studies about use of bevacizumab alone or in combination with other therapeutic agents to treat exudative AMD, and 19 studies on the use of myopic CNV.Although bevacizumab is widely used as an anti-VEGF agent for the treatment of exudative AMD, data on its systemic side effects are limited because of studies' short follow-up periods, absence of appropriate controls, limitation in reporting outcomes, and lack of controlled clinical trials in Phase III. Some safety studies demonstrated no difference between bevacizumab and ranibizumab in occurrence of heart attacks or stroke. Conducting proper randomized clinical trials with long-term follow-up is crucial to make sure about efficacy and safety of bevacizumab.

In the present study, silicate mesoporous materials (MCM-41), MCM-41-grafted polyethylenimine (MCM-41@PEI), and succinated PEI containing amine, amide, and acid groups were successfully synthesized and characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller analysis, and X-ray photoelectron spectroscopy. Thermomyces lanuginosa lipase (TLL) was then immobilized onto MCM-41 and polymer-grafted MCM-41 by physical adsorption. Besides, for enzyme immobilization via covalent bonding, glutaraldehyde (GLU), and hexamethylene diisocyanate (HMDI) were used as the bridges for binding the enzyme to supports. The best result was obtained with the immobilized lipase on MCM-41@PEI-GLU. In the study of the enzyme reusability, it was shown that about 83% of the initial activity could be retained after 12 cycles of uses. The immobilized lipase on the selected support was also applied for the synthesis of ethyl valerate. Following 24 h incubation in n -hexane and solvent free media, the esterification percentages were 79% and 67%, respectively.

In this study, we evaluated the antifungal activity of biogenic tellurium nanoparticles (Te NPs) against Candida albicans (ATCC14053). In addition, the effect of these biogenic NPs on squalene monooxygenase activity and the squalene monooxygenase gene (ERG1) expression level was evaluated. Squalene monooxygenase is an important enzyme involved in the synthesis of ergosterol, cholesterol, and phytosterols. Because of the importance of the noted compound, the squalene monooxygenase gene could be considered a good antifungal target. Results showed that biogenic Te NPs had antifungal effect against C. albicans. The minimal fungicidal concentration-minimal inhibitory concentration ratios of the biogenic Te NPs revealed that these NPs exhibited fungicidal effects against the test strain. The results of an enzyme assay using quantitative high-performance liquid chromatography showed squalene accumulation in C. albicans cells because of enzyme inhibition. Real-time PCR analysis showed an increase in the expression of the ERG1 gene in C. albicans cells, which were treated with Te NPs (0.2 mg/mL). It is conclution that Te NPs can inhibit the squalene monooxygenase enzyme, and, as a result, this inhibition phenomenon can cause an increase in the expression level of the ERG1 gene. This is the first report of the anti-Candida effect of biogenic Te NPs and its possible mechanisms.

Nanosuspensions, as a promising strategy to improve the solubility and bioavailability of poorly water soluble drugs, have been widely investigated in recent years. However, no comprehensive work so far has detailed the effect of independent processing/formulation parameters on the quality of the prepared nanosuspension. In the present study, the relations between solvent flow rate, stirring rate of antisolvent and surfactant concentration (i.e., inputs) on size, and polydispersity index (PDI) (i.e., outputs) of an N-acetylcysteine nanosuspension were investigated using artificial neural networks (ANNs). The response surfaces, generated as 3D graphs after ANNs modeling, demonstrated that all the three factors have a reverse effect on size and PDI. The dominant factor appeared to be the concentration of surfactant. Overall, it was found that the optimum formulation (i.e., minimum size and PDI value) is obtained at high values of surfactant concentration, solvent flow rate, and stirring rate (i.e., >0.9 mg/ml and 120 ml/h and 500 rpm, respectively).

Laccase, a blue multicopper oxidase, has recently received considerable attention because of its usefulness in oxidizing phenolic and non-phenolic compounds, as well as its suitability for organic synthesis, environmental pollutant treatment, and other biotechnological applications. This review covers recent studies on the structural properties, occurrence, reaction mechnisms, redox mediators of laccases and their application in organic synthesis procedures, such as dimerization, polymerization, oxidation, and amination. We also present a brief discussion on laccase activity in non-aqueous media. Given that the development of green protocols for the synthesis of pure compounds is one of the main goals of sustainable chemistry, the exploitation of laccases is expected to remain one of the most popular directions in future biocatalysis research.

Fe 3 O 4 /ZnO core/shell magnetic nanoparticles in 1:1 and 1:2 molar ratios were prepared and characterized by using X-ray powder diffraction, scanning electron microscopy, thermogravimetric analysis, FT-IR spectra, and flame atomic absorption spectrophotometry. Thermomyces lanuginosa lipase (TLL) was then covalently immobilized on the surface of both supports. An immobilization efficiency and yield of 94 ± 2.5% and 86 ± 3.5%, respectively, were measured for nanoparticles in 1:1 molar ratio of Fe 3 O 4 /ZnO and immobilization efficiency and yield were 89 ± 2.2% and 81 ± 3.1%, respectively, when lipase was bound to the functionalized nanoparticles in 1:2 molar ratio. The obtained result indicated that the immobilization considerably improved thermal, pH, and operational stability of TLL compared to the soluble enzyme. Moreover, the immobilized enzyme and seven other commercially lipases were examined for Micheal addition of active methylene compounds to chalcones. TLL resulted in the highest yield of the related reaction product compared to other enzymes. For further optimization of Micheal reaction conditions, the effect of some organic solvents was also examined and the obtained results revealed that hydrophobic solvents were more suitable than others.

The aim of this study was to develop a microemulsion system as a medium for laccase-catalyzed reactions. Phase behavior studies were conducted by constructing partial pseudo-ternary phase diagrams for systems comprising of cetyltrimethylammonium bromide (CTAB), various organic solvents as the oil phase (i.e., hexane, cyclohexane, heptane, octane, isooctane, toluene, isopropyl myristate), two co-surfactants (i.e., 1-butanol and 1-hexanol) and citrate buffer solution, at various surfactant/co-surfactant weight ratios (Rsm). A monophasic, transparent, non-birefringent area (designated as microemulsion domain) was seen to occur in some phase diagrams along the surfactant/organic solvent axis, the extent of which was dependent mainly upon the nature of co-surfactant and Rsm. On each phase diagram, three different water-in-oil (w/o) microemulsion systems with less than 50 wt% surfactant mixture and less than 20 wt% of aqueous phase were selected for laccase loading and activity measurements. Results revealed that the catalytic activity of laccase in CTAB-based w/o microemulsions decreased considerably, compared with its activity in the buffer solution, the extent of which depended upon the type of component and their compositions in the microemulsions. It was suggested that the conformational changes due to the electrostatic interactions between the cationic head group of CTAB and the negative enzyme might be the reason for the reduction of laccase activity, once entrapped in the microemulsion.

Purpose: PLGA nanoparticles (NPs) have been extensively investigated as carriers of different drug molecules to enhance their therapeutic effects or preserve them from the aqueous environment. Streptokinase (SK) is an important medicine for thrombotic diseases. Methods: In this study, we used electrospray to encapsulate SK in PLGA NPs and evaluate its activity. This is the first paper which investigates activity of an electrosprayed enzyme. Effect of three input parameters, namely, voltage, internal diameter of needle (nozzle) and concentration ratio of polymer to protein on size and size distribution (SD) of NPs was evaluated using artificial neural networks (ANNs). Optimizing the SD has been rarely reported so far in electrospray. Results: From the results, to obtain lowest size of nanoparticles, ratio of polymer/enzyme and needle internal diameter (ID) should be low. Also, minimum SD was obtainable at high values of voltage. The optimum preparation had mean (SD) size, encapsulation efficiency and loading capacity of 37 (12) nm, 90% and 8.2%, respectively. Nearly, 20% of SK was released in the first 30 minutes, followed by cumulative release of 41% during 72 h. Activity of the enzyme was also checked 30 min after preparation and 19.2% activity was shown. Conclusion: Our study showed that electrospraying could be an interesting approach to encapsulate proteins/enzymes in polymeric nanoparticles. However, further works are required to assure maintaining the activity of the enzyme/protein after electrospray.

Treponema (T.) denticola is one of the key etiological agents in the development of periodontitis. The major outer sheath protein (Msp) of T. denticola has been shown to mediate pathogenesis and to facilitate adhesion of T. denticola to mucosal surfaces. This study aimed to find short polypeptides in the amino acid sequence of Msp which may be immunogenic and might elicit protective antisera against T. denticola. The complete msp sequence was divided into six fragments and the corresponding genes were cloned and expressed. Antisera against the polypeptides were raised in rabbits and fragment 3 (F3), hereinafter called PerioVax3 was the most potent fragment of the Msp in terms of yielding high titer antiserum. An adhesion assay was done to examine the inhibitory effects of antisera on the attachment of T. denticola to human gingival fibroblasts (HGFs) and human fibronectin. Antiserum against PerioVax3 significantly inhibited attachment of T. denticola to the substratum. Also, antiserum against PerioVax3 inhibited detachment of HGFs upon T. denticola exposure. To begin examining the clinical relevance of this work, blood samples from 12 sever periodontitis patients were collected and the sera were used in western blotting against the recombinant polypeptides. Periodontitis patient antisera exclusively detected PerioVax3 in western blotting. The data suggest that PerioVax3 carries epitopes that may trigger humoral immunity against T. denticola, which may protect against its adhesion functions. The complexity of periodontitis suggests that PerioVax3 may be considered for testing as a component of an experimental multivalent periodontal vaccine in further preclinical and clinical studies.

In this work, new polyacrolein/MCM-41 nanocomposites with good phase mixing behavior were prepared through an emulsion polymerization technique. Mesoporous silica was synthesized by in situ assembly of tetraethyl orthosilicate (TEOS) and cetyl trimethyl ammonium bromide (CTAB). The structure and properties of polyacrolein containing nanosized MCM-41 particle (5 and 10 wt%), were investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, Dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N 2 adsorption techniques, and thermogravimetric (TGA) analyses. The SEM images from the final powder have revealed good dispersion of the MCM-41 nanoparticles throughout polymeric matrix with no distinct voids between two phases. The results indicated that the thermal properties of the nanocomposite were enhanced by addition of MCM-41. Thermomyces lanuginosa lipase (TLL) was used as a model biocatalyst and successfully immobilized with polyacrolein and the nanocomposite via covalent bonds with the aldehyde groups. The activity between free enzyme, polyacrolein, and MCM-41 nanocomposite (10 wt%)-immobilized TLL was compared. The immobilized lipase with the nanocomposite shows better operational stability such as pH tolerance, thermal and storage stability. In addition, the immobilized lipase with the nanocomposite can be easily recovered and retained at 74% of its initial activity after 15 time reuses.

Nanoparticles of ultra low molecular weight chitosan (ULMWCS)/hyaluronic acid (HA) were prepared by ion gelation. Three independent variables, namely, ratio of concentration of ULMWCS to HA (CS/HA), pH of solution and stirring time were studied to identify their effects on size, polydispersity and zeta potential of prepared nanoparticles using a Box-Behnken design. Results showed that pH and CS/HA have a direct effect on size, while increase of stirring time decreases the size of nanoparticles. Additionally, it was shown that all the independent parameters have direct effects on zeta potential. Also, the minimum polydispersity index was observed at lowest values of CS/HA. The model also predicted that the optimum values are 4.15, 4.14 and 180 (min) for the CS/HA, solution pH and stirring time, respectively. The obtained preparation had a size of 200 nm, polydispersity index of 0.37, and zeta potential of 13.0 mV.

The enzymatic decolorization of 13 synthetic dyes with azo- and anthraquinone-based chemical structures using the purified laccase from Paraconiothyrium variabile was assessed in the presence and absence of 1-hydroxybenzotriazole (HBT) as a laccase mediator. The highest decolorization percentage was found for Acid Red 18 (97%) followed by Direct Red 81 (68.3%), Reactive Yellow 15 (60.2%), and Disperse Blue 56 (58%) after 15 min of incubation in the presence of 0.1 U mL −1 of the enzyme. The use of the laccase-HBT system increased decolorization percentage of Reactive Orange 16, Reactive Black 5, Direct Blue 71, Disperse Red 177, and Acid Yellow 36, while other chemical dyes were not affected by an increase of the HBT concentration. The kinetic parameters of the purified laccase for each textile dye were also calculated. A microtoxicity study with respect to the inhibition of bacterial growth showed a decrease in toxicity of the laccase-treated dye solution.

Organic salts of bismuth are currently used as antimicrobial agents against Helicobacter pylori. This study evaluated the antibacterial effect of elemental bismuth nanoparticles (Bi NPs) using a serial agar dilution method for the first time against different clinical isolates and a standard strain of H. pylori. The Bi NPs were biologically prepared and purified by a recently described method and subjected to further characterization by infrared spectroscopy and anti-H. pylori evaluation. Infrared spectroscopy results showed the presence of carboxyl functional groups on the surface of biogenic Bi NPs. These biogenic nanoparticles showed good antibacterial activity against all tested H. pylori strains. The resulting MICs varied between 60 and 100 μg/ml for clinical isolates of H. pylori and H. pylori (ATCC 26695). The antibacterial effect of bismuth ions was also tested against all test strains. The antimicrobial effect of Bi ions was lower than antimicrobial effect of bismuth in the form of elemental NPs. The effect of Bi NPs on metabolomic footprinting of H. pylori was further evaluated by (1)H NMR spectroscopy. Exposure of H. pylori to an inhibitory concentration of Bi NPs (100 μg/ml) led to release of some metabolites such as acetate, formic acid, glutamate, valine, glycine, and uracil from bacteria into their supernatant. These findings confirm that these nanoparticles interfere with Krebs cycle, nucleotide, and amino acid metabolism and shows anti-H. pylori activity.

Novel Mannich bases of 7-piperazinylquinolones with kojic acid and chlorokojic acid were designed as new quinolone antibacterials. All compounds showed significant in vitro antibacterial activity against both Gram-positive and Gram-negative bacteria. Particularly, chlorokojic derivative 2b was the most potent compound against Staphylococcus aureus and Pseudomonas aeruginosa (MIC values ≤0.19 μg/mL). Its activity was 4–8 times more than that of standard drug norfloxacin. The molecular docking study of compound 2b further supported the molecular basis of the designed compounds.

The ascomycete Acremonium strictum was used for the biotransformation of methyltestosterone (1), a pharmaceutical steroid substance, into some steroid derivatives (6β-hydroxy-17α-methyltestosterone (2), 6β,12β-dihydroxy-17α-methyltestosterone (3), 7β-hydroxy-17α-methyltestosterone (4), 6β,17β-dihydroxy-17α-methylandrosta-1,4-dien-3-one (5), and 3,17β-dihydroxy-17α-methylestra-1,3,5(10)-triene (6). The fermentation was carried out in Sabouraud-dextrose broth (SDB) supplemented with 1 mM of the substrate, and the temperature and aeration rate were adjusted to 30°C and 150 rpm, respectively. The biotransformation characteristics observed were hydoxylations at C-6β, C-7β, and C-12β, 1,2-dehydrogenation, and ring A aromatization. The best fermentation conditions, such as temperature, substrate concentration, pH, incubation period, and aeration, were found to be 25°C, 1 mM, pH 6.5, 6 days, and 150 rpm, respectively, for maximum biotransformation of 1.

Magnetic nanoparticles (MNPs) were prepared by co-precipitation of Fe+3/Fe+2 (2:1; molar ratio) with a mean size of 40 ± 5 nm. Scanning electron microscopy, dynamic light scattering, X-ray diffraction, vibrating sample magnetometer and thermogravimetric analysis were used to characterise the MNPs. The MNPs and also hydroxylated nonporous glass beads were similarly functionalised with the aid of glutaraldehyde to be cross-linked to lipase originated from Thermomyces lanuginosus (TLL). The yield and efficiency for immobilised lipase on the MNPs were calculated as 72 ± 2.4 and 63 ± 3.5%, whereas a yield and efficiency of 60 ± 2.1 and 55 ± 4.1%, respectively, were measured for the corresponding parameters of the immobilised enzyme on the glass beads. When the immobilised TLL was compared with its free form, Michaelis–Menten kinetics indicated an insignificant change in the Michaelis constant (K m) and a drastic decrease in the maximum substrate conversion rate (V max). The immobilised TLL and six other commercial lipases were then checked for regioselective acetylation of prednisolone. The highest and lowest yields of the product were observed for Novozym 435 and immobilised TLL on the glass beads, respectively. Immobilised TLL retained its bioacetylation activity of prednisolone in five successive catalytic processes.

A series of novel 3-(1,2,4-triazol-1-yl)flavanones were synthesized based on the N-phenethylazole pharmacophore of azole antifungals. The results of antifungal assay revealed that 4′-fluoroflavanone derivative 4c exhibited the best profile of activity against Candida and Saccharomyces strains. Compound 4c was 4–16 times more potent than reference drug fluconazole against Candida albicans and Saccharomyces cerevisiae. The molecular docking study with lanosterol 14α-demethylase, in silico toxicity risks and drug-likeness predictions were used to better define of title compounds as antifungal agents. The favorable drug-like property of compound 4c makes 3-(1,2,4-triazol-1-yl)flavanone prototype as a promising lead for the future development of azole antifungal agents.

Although a great number of studies may be found in literature about the parameters affecting the size of chitosan nanoparticles, no systematic work so far has detailed the factors affecting the polydispersity of chitosan as an important factor determining the quality of many preparations. Herein, using artificial neural networks (ANNs), four independent variables, namely, pH and concentration of chitosan solution as well as time and amplitude of sonication of the solution were studied to determine their influence on the polydispersity of solution. We found that in an ultrasound prepared nanodispersion of chitosan, all the four input parameters have reverse but non-linear relation with the polydispersity of the nanoparticles.

An extracellular haloalkaliphilic thermostable α-amylase producing archaeon was isolated from the saltwater Lake Urmia and identified as Halorubrum xinjiangense on the basis of morphological, biochemical, and molecular properties. The enzyme was purified to an electrophoretically homogenous state by 80 % cold ethanol precipitation, followed by affinity chromatography. The concentrated pure amylase was eluted as a single peak on fast protein liquid chromatography. The molecular mass of the purified enzyme was about 60 kDa, with a pI value of 4.5. Maximum amylase activity was at 4 M NaCl or 4.5 M KCl, 70 °C, and pH 8.5. The K m and V max of the enzyme were determined as 3.8 mg ml(-1) and 12.4 U mg(-1), respectively. The pure amylase was stable in the presence of SDS, detergents, and organic solvents. In addition, the enzyme (20 U) hydrolyzed 69 % of the wheat starch after a 2-h incubation at 70 °C in an aqueous/hexadecane two-phase system.

Purpose Artificial neural networks (ANNs) are used to optimize a formulation of poly(lactic acid) (PLA) nanoparticles containing hydrophobic drug molecules through a study of the critical parameters affecting nanoparticle size.

Quinolone class of antibacterial agents has considerable attention to find new useful antibacterial agents. Therefore, a series of N-substituted piperazinylquinolones bearing (5-nitrofuran-2-yl)methyl moiety were synthesized and evaluated against a variety of bacteria. The methylene-bridged nitrofuran functionality has been recently used in oxazolidinone class of antibacterial agents containing piperazinyl moiety by introducing ranbezolid as a 5-nitrofuran analog of eperzolid. The results of antibacterial evaluation revealed that the influence of (5-nitrofuran-2-yl) attachment to the 7-piperazinylquinolones against different bacterial species depends on the type of substituents at the N-1 and C-8 positions. Better results were obtained with ethyl at N-1 and CF at C-8 in the term of activity against Bacillus subtilis and E. coli. While, the optimum activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia was entailed by a molecule possessing cyclopropyl at N-1 and CH at C-8.

Laccase, the blue oxidase enzyme with high potency in green synthesis and biodegradation of phenolic compounds, was immobilized by means of chitosan nanoparticles (CS-NPs) on the surface of activated glass beads. Decolorization of Congo red, a harmful industrial dye, was accomplished with nanoparticulated immobilized laccase, directly attaching enzyme on the surface of the glass beads, as well as the free enzyme in order to assess the decolorization activity of immobilized and non-immobilized laccase. Glass surface functionalization was achieved by using chemicals such as sodium hydroxide, 3-aminopropyltriethoxysilane (APES), and glutaraldehyde. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) were used for characterizing enzyme-associated CS-NPs, made by the ion gelation method. Fourier Transform Infrared Spectroscopy (FT-IR) was carried out to identify the attached chemical groups on the surface of the glass beads. Immobilization yields for nanoparticulated and non-nanoparticulated enzymes were 75 ± 4.2 and 68.6 ± 6.4%, respectively whereas, immobilization efficiency for nanoparticulated and non-nanoparticulated laccases were calculated as 40.1 ± 3.4 and 32.2 ± 7.5%, respectively. The applied method for immobilization resulted in increased thermal stability, reusability, and lifetime of the enzyme. Thermal stability of the nanoparticulated immobilized enzyme increased up to near boiling temperature. In addition, 98% of initial decolorization activity of the nanoparticulated immobilized enzyme was retained after 25 successive cycles.

Purified laccase from the soil ascomycete, Paraconiothyrium variabile was employed in the degradation of 7 benzodiazepine substances in the absence and presence of the enzyme mediators, 1-hydroxybenzotriazole (HBT), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), 2,6-dimethoxyphenol (DMP), and vanillic acid (VA). In the absence of a laccase mediator, the original concentrations of 10 μg mL(-1) of nitrazepam, alprazolam, diazepam, and oxazepam decreased by 27.3%, 45.6%, 18.6% and 18.7%, respectively, after 48 h treatment using the purified enzyme, whereas the removal percentages for clobazam, chlordiazepoxide, and lorazepam were only 5.6%, 3.6%, and 4.1%, respectively. Among the laccase mediators, HBT was the most efficient compound, increasing the degradation percentages of nitrazepam, alprazolam, diazepam, and oxazepam to 73%, 88.1%, 61.4%, and 71.2%, respectively. The removal percentages of clobazam, chlordiazepoxide, and lorazepam was increased to 8.2%, 4.7%, and 6.5%, respectively, when the laccase-HBT system was used. The data presented suggest that the laccase-mediated system has potential for the elimination of some benzodiazepines in aqueous solution.

Endothelial dysfunction is initial and critical step of atherosclerosis. Impaired bioavailability of endothelial nitric oxide synthase (eNOS) is one of the main reasons of endothelial dysfunction. Improving bioavailability of eNOS by increasing its expression or activity using statins is an effective therapeutic strategy in restoring endothelial dysfunction. In this study, simvastatin (SIM) as a poorly water-soluble drug was loaded in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (SIM-PLGA-NPs). NPs were then conjugated with mZD7349 peptide (mZD7349-SIM-PLGA-NPs) and directed against vascular cell adhesion molecule 1 (VCAM-1). In vitro evaluation of the NPs for targeted delivery of SIM was performed on activated Human Umbilical Cord Vascular Endothelial Cells (HUVECs) by tumor necrosis factor alpha (TNF-α). Effect of mZD7349-SIM-PLGA-NPs and SIM-PLGA-NPs was compared on eNOS phosphorylation (ser-1177). Results of western blot showed SIM post-treatment increased significantly phosphor-eNOS (Ser1177) expression but no total eNOS expression. The study showed that mZD7349-SIM-PLGA-NPs have particle size, zeta potential value, polydispersity index (PDI) and encapsulation efficacy % of 233±18nm, -9.6±1.1mV, 0.59±0.066 and 69±17.3%, respectively. Also phosphor-eNOS (Ser1177) expression in activated HUVECs treated with mZD7349-SIM-PLGA-NPs was significantly (p

An enzyme immobilized on a mesoporous silica nanoparticle can serve as a multiple catalyst for the synthesis of industrially useful chemicals. In this work, MCM-41 nanoparticles were coated with polyethylenimine (MCM-41@PEI) and further modified by chelation of divalent metal ions (M = Co2+, Cu2+, or Pd2+) to produce metal-chelated silica nanoparticles (MCM-41@PEI-M). Thermomyces lanuginosa lipase (TLL) was immobilized onto MCM-41, MCM-41@PEI, and MCM-41@PEI-M by physical adsorption. Maximum immobilization yield and efficiency of 75 ± 3.5 and 65 ± 2.7% were obtained for MCM@PEI-Co, respectively. The highest biocatalytic activity at extremely acidic and basic pH (pH = 3 and 10) values were achieved for MCM-PEI-Co and MCM-PEI-Cu, respectively. Optimum enzymatic activity was observed for MCM-41@PEI-Co at 75 °C, while immobilized lipase on the Co-chelated support retained 70% of its initial activity after 14 days of storage at room temperature. Due to its efficient catalytic performance, MCM-41@PEI-Co was selected for the synthesis of ethyl valerate in the presence of valeric acid and ethanol. The enzymatic esterification yield for immobilized lipase onto MCM-41@PEI-Co was 60 and 53%, respectively, after 24 h of incubation in n-hexane and dimethyl sulfoxide media.

Enzymatic elimination of synthetic dyes, one of the most environmentally hazardous chemicals, has gained a great interest during the two last decades. The present study was performed to evaluate the decolorization and detoxification potential of the purified laccase of Paraconiothyrium variabile in both non-assisted and hydroxybenzotriazole-aided form against six azo dyes. The obtained results showed that Acid Orange 67, Disperse Yellow 79, Basic Yellow 28, Basic Red 18, Direct Yellow 107, and Direct Black 166 were decolorized up to 65.3, 53.3, 46.7, 40.7, 34, and 26.2 %, respectively, after 1 h treatment with laccase (0.5 U/mL). Addition of HBT up to 5 mM enhanced decolorization percent of all the investigated dyes. The results of kinetic study introduced the monoazo dye of Acid Orange 67 as the most suitable substrate for laccase with K m of 0.49 mM and V max of 189 mmol/min/mg. Evaluation the toxic effect of laccase-treated dye sample based on the growth inhibition of standard bacterial strains revealed decrease in toxicity of all applied dyes after treatment by laccase. Application of the P. variabile laccase as biocatalyst efficiently decreased the toxicity of all studied synthetic azo dyes.

Background: Association between thrombosis pathogenesis and inflammatory conditions has been reported. Also inflammatory biomarkers have been proposed for prediction of thrombosis events. Objectives: Effects of different methods of heparin administration (subcutaneous vs continuous infusion) as thromboprophylaxis on the biomarkers of thrombosis have been evaluated. Methods: Serum levels of hsCRP, IL-10 and P-selectin as the biomarkers of thrombosis were measured at baseline, days 3 and 7 during the patients’ hospitalization period. Results: Changes in the serum levels of thrombosis biomarkers (hsCRP, IL-10 and P-selectin) were comparable between the subcutaneous and continuous infusion groups. Conclusion: Both subcutaneous injection and continuous infusion of heparin as thromboprophylaxis showed same effects on the thrombosis biomarkers.

The purpose of this study was to determine major factors impacting the size of simvastatin (SIM)-loaded poly(d, l-lactic-co-glycolide) (PLGA) nanoparticles (NPs) that was prepared using electrospraying. Three variables including concentration of polymer and salt as well as solvent flow rate were used as input variables. Size of NPs was considered as output variable. For the first time, our findings using a systematic and experimental approach, showed the importance of salt concentration as the dominant factor determining the size with a sharp and reverse effect. Optimum formulation (i.e., flow rate 0.08 mL h−1, polymer concentration 0.7 w/v %, and salt concentration 0.8 mM) was then evaluated for aqueous solubility, encapsulation efficiency, particle size, in vitro drug release pattern and cytotoxicity. A very appreciable encapsulation efficiency (90.3%) as well as sustained release profile, considerable enhancement in aqueous solubility (∼5.8 fold) and high IC50 (>600 µM of SIM-loaded PLGA NPs) indicated PLGA as a promising nanocarrier for SIM. The optimum formulation had particle size, zeta potential value, polydispersity index (PDI) and drug loading of 166 nm, +3 mV, 0.62 and 9%, respectively. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43602.

Microbial biotransformation of steroids is not a new concept, but most studies in this field have focused on fungal and bacterial systems. Microalgae, despite their photosynthetic ability and immense biodiversity, have not received much attention in this aspect until recently. Since the publication of the first article on microalgal biotransformation of steroids about 20 years ago, there have been many reports describing different modifications, including hydroxylation, reduction, side-chain degradation, and isomerization introduced by these microorganisms on estrane, androstane, and pregnane derivatives. On the other hand, the development of new large-scale cultivation systems, the adaptation of existing fermentation techniques to microalgae, and the introduction of microalgal genetic manipulation methods have made these organisms promising candidates for a wide range of biotechnological processes, including biotransformations. In this review, we have summarized the steroid transformation patterns of several microalgal strains and present a perspective of the future trends in microalgal biotechnology, including the possibility of adapting relatively new techniques, such as organic media catalysis and cell immobilization, to this specific field.

Contributing reviewers The editor of DARU Journal of Pharmaceutical Sciences would like to thank all our reviewers who have contributed to the journal in Volume 23 (2015).

usc A multifunctional nanocarrier with multilayer core-shell architecture was prepared by chemical modification of Fe3O4 magnetic nanoparticle (MNPs) with acrolein-styrene-polyethyleneimine (AL-St-PEI) via covalent bonding. MNPs were prepared by co-precipitation method, and then, thiol functionalized (MNPs-SH) were synthesized by treating MNPs with the (3-mercaptopropyl) trimethoxysilane. Subsequently, the copolymerization of St and AL was performed in the presence of the MNPs-SH and butyrolactam by thiol-lactam initiated radical polymerization. Finally, PEI was covalently bounded to the aldehyde groups on the surface of AL-St copolymer. The AL-St-PEI MNPs were investigated by FTIR, XRD, TGA, SEM and TEM. The drug release from AL-St-PEI MNPs was evaluated using doxorubicin as the model anticancer. Furthermore, to determine the effect of drug structure in the release profile from the modified MNPs, some lipophilic model drugs were studied in loading and release study. It was found that the nature of the drugs affect the release profile. The in vitro release modeling demonstrated that doxorubicin release is described by zero-order mechanism while release of lipophilic model drugs is controlled by fickian diffusion. Refereed/Peer-reviewed

Highlights: ► Biosynthesis of rod shape tellurium nanoparticles with a hexagonal crystal structure. ► Extraction procedure for isolation of tellurium nanoparticles from Bacillus sp. BZ. ► Extracted tellurium nanoparticles have good bactericidal activity against some bacteria. -- Abstract: In this study, a tellurium-transforming Bacillus sp. BZ was isolated from the Caspian Sea in northern Iran. The isolate was identified by various tests and 16S rDNA analysis, and then used to prepare elemental tellurium nanoparticles. The isolate was subsequently used for the intracellular biosynthesis of elemental tellurium nanoparticles. The biogenic nanoparticles were released by liquid nitrogen and purified by an n-octyl alcohol water extraction system. The shape, size, and composition of the extracted nanoparticles were characterized. The transmission electron micrograph showed rod-shaped nanoparticles with dimensions of about 20 nm × 180 nm. The energy dispersive X-ray and X-ray diffraction spectra respectively demonstrated that the extracted nanoparticles consisted of only tellurium and have a hexagonal crystal structure. This is the first study to demonstrate a biological method for synthesizing rod-shaped elemental tellurium by a Bacillus sp., its extraction and its antibacterial activity against different clinical isolates.

In the pursuit of novel antibacterial agents with the 2-thiazolylimino-4-thiazolidinone as a core structure, a series of 5-nitro-heteroarylidene and 5-(2-oxoindolin-3-ylidene) analogs of 2-thiazolylimino-5-arylidene-4-thiazolidinone were synthesized and their antibacterial activities were evaluated against some strains of Gram-positive and Gram-negative bacteria, as well as Helicobacter pylori strains. Biological data indicated that 5-nitrofuran analog 5a and 5-nitroimidazole analog 7a containing no substitutions on the thiazole ring were the most potent compounds.

The production of an extracellular lipase from the newly isolated Stenotrophomonas maltophilia was optimized via the statistical design method. During a screening program, the microorganism was isolated from soil samples, according to lipolytic activity on nutrient agar medium supplemented with Rhodamine B. It was identified using morphological and biochemical properties as well as 16S rDNA sequencing analysis. After the initial screening of 10 factors of the medium components, using Plackett–Burman design, results showed that four of them, included olive oil, peptone, yeast extract, and ferrous sulfate, exhibited significant effects on the lipase production by S. maltophilia . The level of each factor was subjected to optimization by using the Box–Behnken technique, and a 9.1-fold enhancement of lipase productivity (from 500 U/ml to 4559 U/ml) was achieved overall in the presence of optimum levels of the effective factors. Forty-three percent of capsaicin (initial concentration of 500 mg/L) was converted to vanillylamine after treatment with the optimized medium (lipase activity 4559 U/ml) for 18 h.

With the aim of finding new bioactive compounds, a series of phenoxyacetophenone derivatives 2 were designed and synthesized as oxygen analogs of dihydrochalcones. Also, phenoxyacetophenones were converted to (Z)-oxime derivatives 3 and their geometry were characterized by 1H-NMR spectroscopy. The in vitro antifungal activity of compounds 2 and 3 was evaluated against Candida albicans, Candida glabrata, Saccharomyces cerevisiae, and Aspergillus niger using micro-dilution method. In general, oxime derivative 3d containing 4-fluorophenoxy moiety showed comparable or more potent antifungal activity (MICs = 15.63–31.25 μg/mL) with respect to the reference drug fluconazole against all tested yeasts. In addition, the antileishmanial activity of title compounds was determined against pormastigote form of Leishmania major. All compounds showed mild growth inhibitory activity against promastigotes. The most active compound was unsubstituted phenoxyacetophenone 2a (IC50 = 80 μg/mL). To anticipate the potential use as drugs, the target compounds were evaluated in their drug-like properties. The in silico values of molecular descriptors for bioactive compounds 2a and 3d revealed that these compounds are within the range set by Lipinski’s ‘Rule of 5’ and show no violation of these rules. Moreover, bioactive compounds 2a and 3d are supposed to be non-mutagenic and non-tumorigenic, with no irritating or reproductive effects.

The pharmacokinetic properties of chitosan nanoparticles have been shown to mainly depend on its particle size. The aim of this study was to concurrently evaluate and model the effective parameters, namely, chitosan concentration, buffer pH, amplitude and time of sonication, on the particle size of chitosan nanoparticles. Chitosan solutions were prepared and sonicated with different values for the above mentioned parameters. The data were then modeled using artificial neural networks (ANNs). The results illustrated that all four input parameters affect the size of prepared chitosan nanoparticles. While a reverse effect was observed between the size and the buffer pH as well as time and amplitude of sonication, the concentration was found to directly influence the particle size. The optimum condition to obtain the minimum size of nanoparticles in the range of 50-200 nm was found to be high values of pH and sonication time (i.e. approximately 4.9 and 500 s, respectively) and amplitude values of more than ~55.

The present study aimed at evaluating the ability of some isolated cyanobacterial and microalgal strains for the removal of ρ-chlorophenol (ρ-CP), an environmentally harmful contaminant. To identify the most efficient species, a screening program was carried out using 15 microalgal and cyanobacterial strains. Among them, Tetraselmis suecica was able to remove 67 % of the ρ-chlorophenol at an initial concentration of 20 mg L−1 from the medium within a 10-day period. The efficacy of the process was dependent on the ρ-chlorophenol concentration. At concentrations above 60 mg L−1 of the pollutant, no removal was observed due to the inhibitory effect of ρ-chlorophenol on the T. suecica cells. The effect of cell immobilization in alginate beads on T. suecica removal capacity was also examined. Using this technique, the removal efficacy for the initial ρ-CP concentration of 20 mg L−1 increased up to 94 %.