Quality by Design for Development,Optimization and Characterization of Brucine Ethosomal Gel for Skin Cancer Delivery

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (3²) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.     

Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design,Synthesis and In-Vitro Biological Evaluation

A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage.     

Nonlinear Axisymmetric Deformation Model for Structures of Revolution

An axisymmetric formulation for modeling three-dimensional deformation of structures of revolution is presented. The axisymmetric deformation model is described using the cylindrical coordinate system. Large displacement effects and material nonlinearities and anisotropy are accommodated by the formulation. Mathematical derivation of the formulation is given, and an example is presented to demonstrate the capabilities and efficiency of the technique compared to the full three-dimensional model.     

Oscillation criteria of second order half linear delay dynamic equations on time scales

In this paper, we establish some new oscillation criteria for a non autonomous second order delay dynamic equation

$${\left( {r\left( t \right)g\left( {{x^\Delta }\left( t \right)} \right)} \right)^\Delta } + p\left( t \right)f\left( {x\left( {\tau \left( t \right)} \right)} \right) = 0,$$

on a time scale T. Oscillation behavior of this equation is not studied before. Our results not only apply on differential equations when T=?, difference equations when T=? but can be applied on different types of time scales such as when T=q^? for q > 1 and also improve most previous results. Finally, we give some examples to illustrate our main results.

     

HgI2@CsI core/shell nanoparticles: Synthesis,characterization, and application in photosensors

Due to their excellent characteristics such as carrier transport ability, high electrical conductivity, and mobility, core/shell nanostructure photovoltaic devices have received a lot of interest. In this study, HgI₂@CsI core/shell nanoparticles were synthesized by using two-step pulsed laser ablation in liquid (PLAL) at laser fluences of 12.7 and 33.1 J/cm². The structural and optical properties of the samples were examined using X-ray diffraction (XRD), zeta potential (ZP), energy dispersive X-ray (EDX), transmission electron microscope (TEM), UV–Vis absorption, and photoluminescence spectra. The XRD data conforms to the formation of cubic CsI and tetrahedral and orthorhombic HgI₂. The zeta potential results show that the sample prepared at 33.1 J/cm² has the highest stability. TEM images show the formation of core-shell morphology and the thickness of the shell depends on the laser fluence. UV–Vis results show that the band gap of the core/shell was 3.22 and 3.23 eV for 12.7 and 33.1 J/cm², respectively. The fluorescence spectra show two emission peaks for two laser fluences. The current-voltage characteristics of the HgI₂@CsI/Si heterojunction were measured at dark and illumination, and the maximum On/Off ratio was about 167 for a photodetector prepared at 12.7 J/cm². The figures of merit of the photodetectors, including responsivity, external quantum efficiency, and detectivity, are measured at room temperature. A responsivity as high as 0.7 W/A at 400 nm was obtained for a photodetector fabricated at 12.7 J/cm².     

Synthesis and Antitumor Activity of New Polysubstituted Thiophenes and 1,3,4‐Thiadiazoles Incorporating 2,6‐Pyridine Moieties

The versatile multifunctional unreported pyridine‐2,6‐bis(2‐cyano‐N‐phenyl‐3‐oxopropanethioamide) ( 3 ) was prepared starting from pyridine‐2,6‐bis‐(3‐oxopropanenitrile) ( 1 ). Several new series of polysubstituted thiophenes and 1,3,4‐thiadiazoles incorporating 2,6‐pyridine moiety were efficiently synthesized. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human cancer cell lines: hepatocellular liver carcinoma (HEPG2) and Caucasian breast adenocarcinoma (MCF‐7). Some of the newly synthesized compounds exhibited better activity than doxorubicin as a reference drug.     

Electrical Properties of Polymethylmethacrylate Polymer Dispersed Liquid Crystals*

The effect on the electrical properties of polymethylmethacrylate polymer containing liquid crystal as dispersed molecules is investigated in the temperature range 30-100°C and the frequency ange from 100 Hz to 10 kHz. It is found that increasing the liquid crystal content enhances the ac-impedance, decreases the ac-loss conductivity and decreases the value of the dielectric constant. The decrease in the ac-impedance with increasing frequency is associated with a dramatic increase in the ac-loss conductivity at frequencies higher than 1 kHz. The decrease in the ac-conductivity with increasing the dispersed liquid crystal phase is attributed to the reduction of the mobility of the charge carriers. Thus, the dielectric property of the system improves.     

Oligosaccharide Analogues of Polysaccharides. Part 1. Concept and synthesis of monosaccharide-derived monomers

It is proposed to study the influence of interresidue H-bonds on the structure and properties of polysaccharides by comparing them to a series of systematically modified oligosaccharide analogues where some or all of the glycosidic O-atoms are replaced by buta-1,3-diyne-1,4-diyl groups. This group is long enough to interrupt the interresidue H-bonds, is chemically versatile, and allows a binomial synthesis. Several approaches to the simplest monomeric unit required to make analogues of cellulose are described. In the first approach, allyl α-D -galactopyranoside ( 1 ) was transformed via 2 and the tribenzyl ether 3 into the triflate 4 (Scheme 2). Substitution by cyanide (→ 5–7 ) followed by reduction with DIBAH led in high yield to the aldehyde 9 , which was transformed into the dibromoalkene 10 and the alkyne 11 following the Corey-Fuchs procedure (Scheme 3). The alkyne was deprotected via 12 or directly to the hemiacetal 13 . Oxidation to the lactone 14 , followed by addition of lithium (trimethylsilyl)acetylide Me₃SiC?CLi/CeCl₃ (→ 15 ) and reductive dehydroxylation afforded the disilylated dialkyne 16 . The large excess of Pd catalyst required for the transformation 11 → 13 was avoided by deallylating the dibromoalkene 10 (→ 17 → 18 ), followed by oxidation to the lactone 19 , addition of Me₃SiC?CLi to the anomeric hemiketals 20 (α-D /β-D 7:2), dehydroxylation to 21 , and elimination to the monosilylated dialkyne 22 (Scheme 3). In an alternative approach, treatment of the epoxide 24 (from 23 ) with Me₃SiC?CLi/Et₂AlCl according to a known procedure gave not only the alkyne 27 but also 25 , resulting from participation of the MeOCH₂O group (Scheme 4). Using Me₃Al instead of Et₂AlCl increased the yield and selectivity. Deprotection of 27 (→ 28 ), dibenzylation (→ 29 ), and acetolysis led to the diacetate 30 which was partially deacetylated (→ 31 ) and oxidized to the lactone 32 . Addition of Me₃SiC?CLi/TiCl₄ afforded the anomeric hemiketals 33 (α-D /β-D 3:2) which were deoxygenated to the dialkyne 34 . This synthesis of target monomers was shortened by treating the hydroxy acetal 36 (from 27 ) with (Me₃SiC?C)₃Al (Scheme 5): formation of the alkyne 37 (70%) by fully retentive alkynylating acetal cleavage is rationalised by postulating a participation of HOC(3). The sequence was further improved by substituting the MeOCH₂O by the (i-Pr)₃SiO group (Scheme 6); the epoxide 38 (from 23 ); yielded 85% of the alkyne 39 which was transformed, on the one hand, via 40 into the dibenzyl ether 29 , and, on the other hand, after C-desilylation (→ 41 ) into the dialkyne 42 . Finally, combined alkynylating opening of the oxirane and the 1,3-dioxolane rings of 38 with excess Et₂Al C?CSiMe₃ led directly to the monomer 43 which is thus available in two steps and 77% yield from 23 (Scheme 6).     

Determination of traces of streptomycin and related antibiotics by adsorptive stripping voltammetry

Adsorptive stripping voltammetry provides sensitive determinations of trace amounts of the saccharide-related antibiotics, streptomycin, erythromycin and novobiocin. A static mercury drop electrode is immersed in a stirred alkaline solution of the drug for a fixed time (60–300 s) at a suitable potential, and the adsorbed species is then stripped in the linear-scan or differential-pulse mode. The preconcentration potentials and stripping peak potentials (vs. Ag/AgCl) are, respectively, ?1.0 V and ?1.58 V for streptomycin, ?0.9 V and ?1.2 V for erythromycin, and ?1.0 V and ?1.38 V for novobiocin. The interfacial behavior is discussed. Short preconcentration periods suffice to quantity streptomycin, novobiocin, and erythromycin down to the 7 × 10^?10 M, 2.5 × 10^?9 M, and 1.3 × 10^?8 M levels, respectively. Streptomycin added to urine can be quantified after simple dilution.     

A Novel Curcumin Arginine Salt: A Solution for Poor Solubility and Potential Anticancer Activities

Curcumin is a natural polyphenolic compound with well-known anticancer properties. Poor solubility and permeability hamper its use as an anticancer pharmaceutical product. In this study, L-arginine, a basic amino acid and a small hydrophilic molecule, was utilized to form a salt with the weak acid curcumin to enhance its solubility and potentiate the anticancer activities of curcumin. Two methods were adopted for the preparation of curcumin: L-arginine salt, namely, physical mixing and coprecipitation. The ion pair or salt was characterized for docking, solubility, DSC, FTIR, XRD, in vitro dissolution, and anticancer activities using MCF7 cell lines. The molecular docking suggested a salt/ion-pair complex between curcumin and L-arginine. Curcumin solubility was increased 335- and 440-fold by curcumin in L-arginine, physical, and co-precipitated mixtures, respectively. Thermal and spectral analyses supported the molecular docking and formation of a salt/ion pair between curcumin and L-arginine. The cytotoxicity of curcumin L-arginine salt significantly improved (p < 0.05) by 1.4-fold, as evidenced by the calculated IC_50%, which was comparable to Taxol (the standard anticancer drug but with common side effects).