Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation. All screened excipients were reported for their P-glycoprotein and cytochrome P450 3A4 (CYP3A4) modulation activity. Ternary and pseudo ternary diagrams were constructed to optimize the system. Peppermint oil and clove oil showed a high emulsification ability. The nature of obtained dispersions was identified to be nanoemulsions. Twenty-four formulations were evaluated for stability, robustness to dilution and self-emulsification efficiency. All formulations showed a very short emulsification time of less than 2 min. The emulsification efficiency was significantly superior at pH 6.8, at which the largest self-emulsifying region was also observed. Eight formulations were selected for further characterization according to cloud point measurement; mean droplet size, poly dispersity index (PDI) and zeta potential determination in addition to in vitro drug release study. All selected formulations showed very high cloud points (70-90oC), ultrafine mean droplet size (12 ±1.4 to 24.5 ± 2.13 nm), very low PDI values (0.015-0.1305) and almost a complete drug release after 12 h. Formulation F15 (Peppermint oil 55% w/w: Cremophor RH40 25% w/w: Labrasol 20% w/w) was selected for further characterization. Its droplet size showed robustness to different dilution folds with different media and its TEM photograph showed spherical particles without any apparent aggregation even after 24 h. Formulation F15 successfully controlled the systolic blood pressure of hypertensive rats for 24 h with the maximum effect was observed after 2 h. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.

Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation. All screened excipients were reported for their P-glycoprotein and cytochrome P450 3A4 (CYP3A4) modulation activity. Ternary and pseudo ternary diagrams were constructed to optimize the system. Peppermint oil and clove oil showed a high emulsification ability. The nature of obtained dispersions was identified to be nanoemulsions. Twenty-four formulations were evaluated for stability, robustness to dilution and self-emulsification efficiency. All formulations showed a very short emulsification time of less than 2 min. The emulsification efficiency was significantly superior at pH 6.8, at which the largest self-emulsifying region was also observed. Eight formulations were selected for further characterization according to cloud point measurement; mean droplet size, poly dispersity index (PDI) and zeta potential determination in addition to in vitro drug release study. All selected formulations showed very high cloud points (70-90oC), ultrafine mean droplet size (12 ±1.4 to 24.5 ± 2.13 nm), very low PDI values (0.015-0.1305) and almost a complete drug release after 12 h. Formulation F15 (Peppermint oil 55% w/w: Cremophor RH40 25% w/w: Labrasol 20% w/w) was selected for further characterization. Its droplet size showed robustness to different dilution folds with different media and its TEM photograph showed spherical particles without any apparent aggregation even after 24 h. Formulation F15 successfully controlled the systolic blood pressure of hypertensive rats for 24 h with the maximum effect was observed after 2 h. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.

A pencil graphite electrode modified with poly (bromocresol green (BCG)) was prepared by electro-polymerization process for the determination of pantoprazole sodium. The surface morphology and structure of poly (BCG) film were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The determination of pantoprazole sodium in Britton–Robinson buffer (pH 7.0) was carried out by square wave adsorptive stripping voltammetric technique. Under optimum conditions, the linear response of the peak with concentration of the cited drug was in the range of 6.6–360×10−8M with limit of detection of 2.2×10−8 M. Moreover, the poly (BCG)-modified electrode has been successfully applied to determine pantoprazole sodium in tablets, vials and during pharmacokinetic studies.

A pencil graphite electrode modified with poly (bromocresol green (BCG)) was prepared by electro-polymerization process for the determination of pantoprazole sodium. The surface morphology and structure of poly (BCG) film were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The determination of pantoprazole sodium in Britton–Robinson buffer (pH 7.0) was carried out by square wave adsorptive stripping voltammetric technique. Under optimum conditions, the linear response of the peak with concentration of the cited drug was in the range of 6.6–360×10−8M with limit of detection of 2.2×10−8 M. Moreover, the poly (BCG)-modified electrode has been successfully applied to determine pantoprazole sodium in tablets, vials and during pharmacokinetic studies.

A pencil graphite electrode modified with poly (bromocresol green (BCG)) was prepared by electro-polymerization process for the determination of pantoprazole sodium. The surface morphology and structure of poly (BCG) film were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The determination of pantoprazole sodium in Britton–Robinson buffer (pH 7.0) was carried out by square wave adsorptive stripping voltammetric technique. Under optimum conditions, the linear response of the peak with concentration of the cited drug was in the range of 6.6–360×10−8M with limit of detection of 2.2×10−8 M. Moreover, the poly (BCG)-modified electrode has been successfully applied to determine pantoprazole sodium in tablets, vials and during pharmacokinetic studies.

The crotonases comprise a widely-distributed enzyme superfamily that has multiple roles in both primary and secondary metabolism. Many crotonases employ oxyanion hole-mediated stabilisation of intermediates to catalyse reaction of coenzyme A (CoA) thioester substrates (e.g., malonyl-CoA, α,β-unsaturated CoA esters) with both nucleophiles and, in the case of enolate intermediates, with varied electrophiles. Reactions of crotonases that proceed via a stabilized oxyanion intermediate include the hydrolysis of substrates including proteins, as well as hydration, isomerization, nucleophilic aromatic substitution, Claisen-type reactions, and cofactor-independent oxidation reactions. The crotonases have a conserved fold formed from a central β-sheet core surrounded by α-helices, which typically oligomerize to form a trimer, or dimer of trimers. The presence of a common structural platform and a mechanism involving intermediates with diverse reactivity implies that the crotonases have considerable potential for biocatalysis and synthetic biology, as supported by pioneering protein engineering studies on them. In this Perspective, we give an overview of crotonase diversity and structural biology, then illustrate the scope of crotonase catalysis and potential for biocatalysis.

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film-coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton-Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1- 120 mM and 5.2-90 mM for RAB sodium and DOM, respectively while SWAdSV was 7.5-803107M and 5– 703107M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binarybinary mixture in synthetic mixtures and biological fluids.

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film-coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton-Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1- 120 mM and 5.2-90 mM for RAB sodium and DOM, respectively while SWAdSV was 7.5-803107M and 5– 703107M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binarybinary mixture in synthetic mixtures and biological fluids.

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film-coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton-Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1- 120 mM and 5.2-90 mM for RAB sodium and DOM, respectively while SWAdSV was 7.5-803107M and 5– 703107M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binarybinary mixture in synthetic mixtures and biological fluids.