Thermosensitive mucoadhesive gel formulation loaded with 5-Fu: cyclodextrin complex for HPV-induced cervical cancer

Human Papilloma Virus (HPV) infections are the major cause of cervical cancers. To achieve a better therapeutic efficacy and patient compliance in the treatment for HPV-induced cervical cancers, anticancer agent 5-fluorouracil has been formulated in a vaginal gel using the thermosensitive polymer Pluronic^® F127 together with alternative mucoadhesive polymers e.g., hyaluronic acid, Carbopol 934 and hydroxypropylmethylcellulose. To increase its aqueous solubility and to achieve the complete release of 5-FU from the gel, the drug was incorporated as its inclusion complex with 1:1 molar ratio with either β-cyclodextrin or hydroxypropyl-β-cyclodextrin. Following the characterization of drug:CD complexes, thermosensitive gel formulations containing different mucoadhesive polymers and the drug in free or complexed form were characterized in vitro by determining the gelation temperature and the rheological behavior of different formulations along with the in vitro release profiles of these formulations in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin accelerated the release of 5-FU with the exception of formulation containing Carbopol 934 as mucoadhesive polymer. As far as rheological properties are concerned, favorable thermosensitive in situ gelling properties were obtained with formulations containing HPMC as mucoadhesive polymer. Complete release of 5-FU from gels were obtained with both complexes of β-CD and HP-β-CD and cytotoxicity studies against HeLa human cervical carcinoma cells demonstrated that 1% 5-FU:CD complexes were equally effective as 1% free 5-FU indicating better therapeutic efficacy with lower dose.     

Photochemical reactions of M(CO)6 (M = Cr,Mo, W) with Ph2P(S)P(S)Ph2

New complexes {M(CO)₄[Ph₂P(S)P(S)Ph₂]} (M = Cr, Mo and W), (1a)–(3a), [(1a), M = Cr; (2a), M = Mo; (3a), M = W] and {M₂(CO)₁₀[-Ph₂P(S)P(S)Ph₂]} (M = Cr, Mo, W), [(1b)–(3b) [(1b), M = Cr; (2b), M = Mo; (3b), M = W]] have been prepared by the photochemical reaction of M(CO)₆ with Ph₂P(S)P(S)Ph₂ and characterized by elemental analyses, f.t.-i.r. and ³¹P-(¹H)-n.m.r. spectroscopy and by FAB-mass spectrometry. The spectra suggest cis-chelate bidentate coordination of the ligand in {M(CO)₄[Ph₂P(S)P(S)Ph₂]} and cis-bridging bidentate coordination of the ligand between two metals in (M = Cr, Mo and W).     

Synthesis of tris(β,β,γ-oximinoalkyl)amines from aliphatic nitro compounds and methyl vinyl ketone

A general strategy for the assembly of previously unknown tris(β,β,γ-oximinoalkyl)amines from aliphatic nitro compounds and methyl vinyl ketone is described. The strategy involves N,N-bis(siloxy)enamines as key intermediates. The latter are accessible by double silylation of alkylnitro compounds. Nickel(II) and copper(II) complexes of tris(β,β,γ-oximinoalkyl)amines are prepared and structurally characterized.     

An Easy Synthesis of Monofluorinated Derivatives of Pyrroles from β-Fluoro-β-Nitrostyrenes

The catalyst-free conjugate addition of pyrroles to β-Fluoro-β-nitrostyrenes was investigated. The reaction was found to proceed under solvent-free conditions to form 2-(2-Fluoro-2-nitro-1-arylethyl)-1H-pyrroles. The effectiveness of this approach was demonstrated through the preparation of a series of the target products in a quantitative yield. The kinetics of a conjugate addition of pyrrole was studied in detail to reveal the substituent effect and activation parameters of the reaction. The subsequent base-induced elimination of nitrous acid afforded a series of novel 2-(2-Fluoro-1-arylvinyl)-1H-pyrroles prepared in up to an 85% isolated yield. The two-step sequence herein proposed is an indispensable alternative to a direct reaction with elusive and unstable 1-Fluoroacetylenes.     

Photochemical reactions of metal carbonyls [M(CO)6 (M = Cr,Mo and W), Re(CO)5Br,Mn(CO)3Cp] with 2-hydroxyacetophenone methanesulfonylhydrazone (apmsh)

Five new complexes, [M(CO)₅(apmsh)] [M = Cr; (1), Mo; (2), W; (3)], [Re(CO)₄Br(apmsh)] (4) and [Mn(CO)₃(apmsh)] (5) have been synthesized by the photochemical reaction of metal carbonyls [M(CO)₆] (M = Cr, Mo and W), [Re(CO)₅Br], and [Mn(CO)₃Cp] with 2-hydroxyacetophenone methanesulfonylhydrazone (apmsh). The complexes have been characterized by elemental analysis, mass spectrometry, f.t.-i.r. and ¹H spectroscopy. Spectroscopic studies show that apmsh behaves as a monodentate ligand coordinating via the imine N donor atom in [M(CO)₅(apmsh)] (1–4) and as a tridentate ligand in (5).     

Effect of ionic environments on the adsorption and diffusion characteristics of serine alkaline protease enzyme in polyethersulfone ultrafiltration membranes

Static adsorption of serine alkaline protease (SAP) enzyme on hydrophobic polyether sulfone (PES) ultrafiltration membranes in different ionic environments was investigated. The amount of SAP adsorbed on membranes was the lowest at its isoelectric point (IEP) where the maximum adsorption was obtained below the IEP of the enzyme. The extent of SAP adsorption in the phosphate buffer solutions including different salts followed the order: (NH4)2HPO4 > KH2PO4 > Na2HPO4-NaH2PO4 (buffer) > CaCl2 > ((NH4)2HPO4 + H2PO4 + CaCl2), which was consistent with the Hofmeister series. The zeta potentials of membranes contacted with the ionic species were calculated by streaming potential measurements and found that the increase in ionic strength decreased the electrical double layer thickness leading to a decrease in adsorption. A model based on mass balance was developed to calculate the diffusion coefficient of SAP in PES membranes. Employing experimental data evaluated in a diffusion cell along with the data of adsorption isotherms, diffusion coefficients of SAP in PES membranes in the presence of different ionic species were calculated. To detect the structural changes occurred, membrane surfaces were analysed by Fourier transform infrared-attenuated total reflectance (FTIR-ATR) measurements.     

Temperature and magnetic field responsive hyaluronic acid particles with tunable physical and chemical properties

We report the preparation and characterization of thiolated-temperature-responsive hyaluronic acid-cysteamine-N-isopropyl acrylamide (HA-CYs-NIPAm) particles and thiolated-magnetic-responsive hyaluronic acid (HA-Fe-CYs) particles. Linear hyaluronic acid (HA) crosslinked with divinyl sulfone as HA particles was prepared using a water-in-oil micro emulsion system which were then oxidized HA-O with NaIO₄ to develop aldehyde groups on the particle surface_. HA-O hydrogel particles were then reacted with cysteamine (CYs) which interacted with aldehydes on the HA surface to form HA particles with cysteamine (HA-CYs) functionality on the surface. HA-CYs particles were further exposed to radical polymerization with NIPAm to obtain temperature responsive HA-CYs-NIPAm hydrogel particles. To acquire magnetic field responsive HA composites, magnetic iron particles were included in HA to form HA-Fe during HA particle preparation. HA-Fe hydrogel particles were also chemically modified. The prepared HA-CYs-NIPAm demonstrated temperature dependent size variations and phase transition temperature. HA-CYs-NIPAm and HA-Fe-CYs particles can be used as drug delivery vehicles. Sulfamethoxazole (SMZ), an antibacterial drug, was used as a model drug for temperature-induced release studies from these particles.     

The use of gold nanoparticles as an effective modifier for the determination of arsenic and antimony by electrothermal atomic absorption spectrometry

Gold nanoparticles (AuNPs) were used as a new chemical modifier for the determination of arsenic and antimony in salt solutions by electrothermal atomic absorption spectrometry. The AuNPs were prepared by reducing chloroauric acid with sodium citrate. The effects of pyrolysis and atomization temperatures, the amounts of interferents and modifier on the sensitivities of arsenic and antimony were investigated. As and Sb remain in the graphite tube up to 1,100°C, which is sufficient for the determination of the two metals in certified reference materials and spiked sea water samples within a 95% confidence level with low RSD (<10%). The detection limits (N?=?10 at 3??) for As and Sb in sea water are 2.3???g?L^-1 and 3.0???g?L^-1, respectively. Almost no background as well as a blank value was detected for AuNPs.

Structure of 4,4′-butane-(1,4,7-three-p-tolylsulphonyl-1,4,7-three amine) diphthalonitrile

Abstract

The crystal structure of the title compound, C₄₁ H₃₅ N₇ O₆ S₃ was determined as monoclinic by single crystal X-Ray diffraction technique. The molecular structure was identified by IR, ¹H-NMR, ¹³C-NMR and elemental analysis. The crystal parameters of this compound are as follows: monoclinic P 2 1/n, a = 12.694(2) Å, b = 26.204(2) Å, c = 13.005(2) Å, β = 102.95(2)°, V = 4216.02(1) Å.³, Z = 4, Dx = 1.289 g/cm³, F(000) = 1704, λ (MoKα) = 0.71070 Å, μ = 0.2 mm^?1. The structure was solved by SHELXS-97 and refined by SHELXL-97. R = 0.06 for 3178 observed reflections with I > 2σ (I).     

Electrochemical adsorption properties and inhibition of copper corrosion in chloride solutions by ascorbic acid: experimental and theoretical investigation

In this study, the effect of ascorbic acid in the electrochemical behavior of copper has been investigated in 3.5 % NaCl solution using potentiodynamic polarization and electrochemical impedance spectroscopy. Current-potential curve and Nyquist diagrams were obtained in different concentrations of ascorbic acid. The surface morphology of copper after its exposure to 3.5 % NaCl solution with and without of ascorbic acid was examined by scanning electron microscopy. The obtained results show that ascorbic acid inhibits corrosion of copper in 3.5 % NaCl solution. The inhibition activity of ascorbic acid increases with a decrease in the concentration of ascorbic acid.