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.     

Syntheses of 1beta-methylcarbapenems bearing 5-methyl-4-hydroxypyrrolidinone

A new series of 1beta-methylcarbapenems 1a-d bearing 5-methyl-4-mercaptopyrrolidinone rings has been prepared and evaluated for in vitro antibacterial activity and pharmacokinetic parameters. Most compounds showed excellent antibacterial activity and high stability to dehydropeptidase-1. We have synthesized optically active 5-methyl-4-hydroxypyrrolidinones from enantiomerically pure aziridine esters.     

Gold(III) complexes with imidazole,benzoxazole, purine and pyrimidine derivatives

Summary The synthesis and characterization of Au^III complexes with several heterocyclic ligands are reported. The compounds have general formula [AuX₃(L)], where L =N-methylimidazole (N-MeIz),N-ethylimidazole (N-EtIz),N-propylimidazole (N-PrIz), benzoxazole (BO), 2-methylbenzoxazole (2-MeBO), 2,5-dimethylbenzoxazole (2,5-diMeBO), 2-amino-pyrimidine (2-APm), 4(6) -hydroxy-pyrimidine [4(6)-hydrPm] or hypoxanthine (Hypox) and X = Cl or Br. Elemental analysis, conductivity measurements and spectral studies were used for the characterization of the complexes. A square-planar geometry withN-bonded heterocyclic ligands is suggested.     

New liquid chromatographic-chemometric approach for the determination of sunset yellow and tartrazine in commercial preparation

A new liquid chromatographic (LC)-chemometric approach was developed for the determination of sunset yellow (SUN) and tartrazine (TAR) in commercial preparations. This approach uses LC and chemometric calibration methods, i.e., classical least-squares (CLS), principal component regression (PCR), and partial-least squares (PLS), simultaneously. The combined LC-chemometric approaches, denoted as LC-CLS, LC-PCR, and LC-PLS, are based on photodiode array (PDA) detection at multiple wavelengths. Optimum chromatographic separation of SUN and TAR with allura red as the internal standard (IS) was obtained by using a Waters Symmetry C18 column, 5 microm, 4.6 x 250 mm, and 0.2 M acetate buffer (pH 5)-acetonitrile-methano-bidistilled water (55 + 20 + 15 + 10, v/v) as the mobile phase at a flow rate of 1.9 mL/min. The LC data sets consisting of the ratios of analyte peak areas to the IS peak area were obtained by using PDA detection at 5 wavelengths (465, 470, 475, 480, and 485 nm). LC-chemometric calibrations for SUN and TAR were separately constructed by using the relationship between the peak-area ratio and the training sets for each colorant. LC-chemometric approaches were tested for different synthetic mixtures containing SUN and TAR in the presence of the IS. These LC-chemometric calibrations were applied to a commercial preparation of the 2 colorants. The experimental results of the LC-chemometric approaches were compared with those obtained by a developed classical LC method using single-wavelength detection.     

Synthese von 4H-Pyrano[2,3-d]pyrimidinen

Summary Good yields of substituted 5-(5R-2-furyl)-4H-pyrano[2,3-d]pyrimidines4 were obtained in the reaction of 2-ethoxymethyleneamino-3-cyano-4H-pyranes2 with ammonia. Compounds2 were prepared by the condensation of the starting 2-amino-5-acetyl-3-cyano-6-methyl-4H-pyranes1 with ethyl orthoformate. Spectral properties of the bicyclic system4 in relation to compounds3 are discussed.

     

Single polymer molecules adsorbed to mica and the oppositely charged polymer/surfactant complexes formed at the air–water interface visualized by atomic force microscopy

In the present study, the structure and morphology of single sodium poly(styrenesulfonate) (PSS) molecules adsorbed to mica surface from the natural aqueous solution is investigated using atomic force microscopy technique. Results show that single PSS molecules are observed which show a morphology of wormlike coils. Meanwhile, single sodium poly(styrenesulfonate) (PSS)/Hexadecyltrimethylammonium bromide (CTAB) complexes deposited on mica from the air–water interface are also observed. However, the PSS/CTA⁺ complexes show different conformations by appearing in the morphology of circular patches. Experimental data are in fair agreement with the theoretical analysis.     

Speciation of arsenic and selenium compounds by ion-pair reversed-phase chromatography with electrothermic atomic absorption spectrometry. Application of experimental design for chromatographic optimisation

An off-line system is proposed consisting of ion-pair reversed-phase liquid chromatography, collections of fractions at the outflow of the column and furnace atomic absorption spectrometry. The so-called system allowed determination of both arsenic and selenium species mainly found in the environment and in mammals (arsenite, arsenate, monomethylarsonate, dimethylarsinate, selenite, selenate, selenocystamine, selenocystine, selenomethionine and selenoethionine). In order to study the retention behaviour of these compounds and to estimate the optimal conditions for the chromatographic separation, central composite designs were used to evaluate the influence of the eluent parameters such as pH, tetrabutylammonium phosphate (TBA) concentration and sodium hydrogenphosphate amounts. The retention factors of each species and the selectivity were established as response criteria. Response surfaces and isoresponse curves were drawn from the mathematical models and enabled one to determine the optimal conditions and to visualise the method robustness. The predicted optimal zone was situated at pH 5.5-6.5, 4.0 mM Na2HPO4 and 3.0-4.0 mM TBA. Regression models suggested linearity for the studied compounds in the range 25-200 microg selenium and arsenic per litre investigated.     

Multiresidue determination of pesticides in drinking and related waters by gas chromatography/mass spectrometry after solid-phase extraction: interlaboratory study

As part of a project funded by the European Commission (EC) for the development and evaluation of multiresidue methods for analysis of drinking and related waters, 15 European laboratories evaluated a method using styrene-divinylbenzene co-polymer solid-phase extraction followed by gas chromatography/mass spectrometry. The main aim of the study was to evaluate whether the method meets the requirements of EC Directive 98/83 in terms of accuracy, precision, and detection limit for 22 pesticides according to the following requirements: limit of detection, < or = 0.025 microg/L; accuracy, expressed as recovery between 75 and 125%; and precision, expressed as repeatability relative standard deviation of the method of < 12.5% and as reproducibility relative standard deviation of the method of < 25%. Analyses for unknown concentrations were performed with fortified commercial bottled and tap waters. All laboratories were able to achieve detection limits of 0.01 microg/L for all pesticides except dimethoate and desisopropylatrazine (0.02 microg/L). The criteria for repeatability were met for all compounds except trifluralin, dimethoate, and lindane in bottled water and chlorpyrifos, dimethoate, and lindane in tap water. The criteria for reproducibility were met for all compounds except trifluralin, dimethoate, and lindane in bottled water and pendimethalin, chlorpyrifos, dimethoate, terbutryn, and lindane in tap water. In terms of accuracy, the method meets the requirements for all pesticides in both matrixes, except for lindane in bottled water and lindane and chlorpyrifos in tap water.     

Helical coordination polymers and cyclic dimers formed from heteroleptic thioether-dipyrrinato copper(II) complexes

Heteroleptic copper complexes containing an acetylacetonato ligand and a thioether derivatized dipyrrinato ligand are shown to form oligomers and polymers in the solid state.     

Effect of water of crystallization on magnetic properties of MgSO4

The object of this paper has been to determine the effect of water of crystallization on magnetic properties of MgSO₄. Changes in the magnetic properties of MgSO₄ in depenedence on the number of waters of crystallization have been established from the magnetic susceptibility changes. The value obtained by measurement differs from that calculated by the additivity law. This disagreement can be explained by the presence of the thermally independent Van Vleck's polarization paramagnetism _p .The paper brings forward calculations of _p values for the individual hydrates of MgSO₄.i H₂O fori=0, 1, ..., 7. Besides, it examines what portion of the polarization paramagnetism _pi of the overall values of _pci is due to the effect of water of crystallization. On the basis of this information the deviation from the spherical symmetry, caused by hydration of the MgSO₄ molecule, has been interpreted.