Inclusion complexes of ketoconazole with beta-cyclodextrin: physicochemical characterization and in vitro dissolution behaviour of its vaginal suppositories

Ketoconazole (KZ) is an imidazole antifungal agent which is administered topically and also orally. KZ is practically insoluble in water. Vaginal candidiasis is a common condition and up to 75% of all women have at least one episode of this infection during their lifetime. The aim of study was to prepare KZ/β-cyclodextrin (β-CD) complex to improve the physicochemical properties of KZ and to investigate the possibility of preparing vaginal suppositories with the complexes. A linear increase in KZ solubility as a function of β-CD concentration was verified using the phase-solubility diagram. The resulting diagram was classified as A_L-type, is generally related to the formation of a soluble complex. Complexes were prepared in a 1:1 molar ratio by different methods, namely freeze-drying, spray-drying, co-evaporation and kneading. Characterization of the complexes prepared was performed by practical yield %, aqueous solubility, active agent amount analyses, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD) and ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy. Characterization studies provided additional evidences of complexation. The paddle method defined in USP31 was used in in vitro dissolution experiments on the prepared vaginal suppositories. It was found that solubility enhancement by preparing KZ/β-CD complexes depends on the type of the preparation method. Dissolution of KZ from complexes was found to be faster than the active agent and the commercial suppositories. This result may be attributed to the interactions between β-CD and active agent, high energetic amorphous state and decrease in the interfacial tension between insoluble active agent and dissolution media.     

Sol–gel synthesis of IPTES and D10H consisting fluorinated silane system for hydrophobic applications

In this study, new fluorinated silane system was prepared by adding hydroxyl terminated Fluorolink D10H oligomer to 3-isocyanatopropyltrietoxysilane. The obtained silane system was independently composed with 3-Glycidyloxypropyltrimethoxysilane and 3-Glycidyloxy-propyltriethoxysilane. Then the prepared two different coating solutions were applied to glass surface by spin-coating method. The chemical bonding between groups in system was investigated by FTIR analysis. The elemental composition of coatings was determined by using EDX analysis. Their structure and surface properties were analyzed by scanning electron microscopy, atomic force microscopy, contact angle measurement and UV–vis spectrophotometer. The amounts of fluorine on the coatings prepared with IPTES-D10H-GLYEO and IPTES-D10H-GLYMO were 33 and 34 %wt, respectively. Transparent coatings with smooth surface and uniform thickness were obtained. The coatings had nanoscale roughness. The contact angles of coatings for water were range from 103° to 110°, and for n-hexadecane were range from 59° to 62°.     

Multiarm star triblock terpolymers via sequential double click reactions

Multiarm star triblock terpolymers were obtained by using two different click reactions sequentially: Cu(I) catalyzed azide–alkyne and Diels–Alder. The synthetic strategy is described as follows: (poly(methyl methacrylate))_n‐(polystyrene)_m‐poly(divinyl benzene)) ((PMMA)_n‐(PS)_m‐polyDVB) multiarm star diblock copolymer was first obtained from an azide–alkyne click reaction of (alkyne‐PS)_m‐polyDVB multiarm star polymer with α‐anthracene‐ω‐azide PMMA (anth‐PMMA‐N₃), followed by a Diels–Alder click reaction of the anthracene groups at the star periphery with α‐maleimide poly (tert‐butyl acrylate) (PtBA‐MI) or α‐maleimide poly(ethylene glycol) (PEG‐MI) leading to target (PtBA)_k‐(PMMA)_n‐(PS)_m‐polyDVB and (PEG)_p‐(PMMA)_n‐(PS)_m‐polyDVB multiarm star triblock terpolymers. The hydrodynamic diameter of individual multiarm star triblock terpolymers were measured by dynamic light scattering (DLS) to be ～24–27 nm in consistent with the atomic force microscopy (AFM) images on silicon substrates. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1557–1564, 2010     

Effect of amine catalysts on preparation of nanometric SiO<Subscript>2</Subscript> particles and antireflective films via sol–gel method

SiO₂ sols were prepared by hydrolysis and condensation reactions of tetraethyl orthosilicate through a one step acid or a two step acid + base catalysis process, in the presence of nitric acid and four different base catalyzers, namely trimethylamine, triethylamine, tripropylamine and tributylamine. Hydrolysis of TEOS was followed by FT-IR analyses. Particle size distributions of the sols were evaluated after predetermined durations in 1–22 days. Particle growth was seen to be faster in amine catalyzed systems than in one step acid catalyzed system. The highest rate of growth was in triethylamine catalyzed system. Glass substrates were dip coated with the prepared SiO₂ sols. Effect of sol aging duration on film thickness and on light transmittance properties of the films was investigated with respect to type of base catalyst. Thicknesses of the films which were measured to be in the range of 100–400 nm, were seen to increase with aging duration of the sols. Triethylamine catalyzed system presented the highest film thickness. Films obtained from one step acid catalyzed system presented an increase of 4.8%; whereas acid + base catalyzed films provided an increase in the light transmittance of 5.7% in the first 4 days of aging. Surfaces of films were examined by FESEM and AFM. The antireflective character of the films was verified by diffuse reflectance analyses.     

Distinguished representations and exceptional poles of the Asai-L-function

Let K/F be a quadratic extension of p-adic fields. We show that a generic irreducible representation of GL(n, K) is distinguished if and only if its Rankin-Selberg Asai L-function has an exceptional pole at zero. We use this result to compute Asai L-functions of principal series representations of GL(2, K), hence completing the computation of these functions for generic representations of this group.     

Poly(cyclohexene oxide)/clay nanocomposites by photoinitiated cationic polymerization via activated monomer mechanism

Poly(cyclohexene oxide) (PCHO)/clay nanocomposites were prepared by in situ photoinitiated activated monomer cationic polymerization. The polymerization of cyclohexene oxide through the interlayer galleries of the clay can provide distribution of the clay layers in the polymer matrix homogenously and results in the formation of PCHO/clay nanocomposites. The exfoliated structures were characterized by X‐ray diffraction spectroscopy, thermogravimetric analysis, transmission electron microscopy, and atomic force microscopy. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5328–5335, 2009     

Steady Flows of Shear-Dependent Oldroyd-B Fluids around an Obstacle

This work is concerned with the study of steady flows of an incompressible viscoelastic fluid of Oldroyd type, with viscosity depending on the second invariant of the rate of deformation tensor in an exterior domain. We establish a result of existence and uniqueness of strong solutions for sufficiently small data and give estimates relating these solutions to those of the corresponding generalized Newtonian fluid.     

Responsive microgrooves for the formation of harvestable tissue constructs

Given its biocompatibility, elasticity, and gas permeability, poly(dimethylsiloxane) (PDMS) is widely used to fabricate microgrooves and microfluidic devices for three-dimensional (3D) cell culture studies. However, conformal coating of complex PDMS devices prepared by standard microfabrication techniques with desired chemical functionality is challenging. This study describes the conformal coating of PDMS microgrooves with poly(N-isopropylacrylamide) (PNIPAAm) by using initiated chemical vapor deposition (iCVD). These microgrooves guided the formation of tissue constructs from NIH-3T3 fibroblasts that could be retrieved by the temperature-dependent swelling property and hydrophilicity change of the PNIPAAm. The thickness of swollen PNIPAAm films at 24 °C was approximately 3 times greater than at 37 °C. Furthermore, PNIPAAm-coated microgroove surfaces exhibit increased hydrophilicity at 24 °C (contact angle θ = 30° ± 2) compared to 37 °C (θ = 50° ± 1). Thus PNIPAAm film on the microgrooves exhibits responsive swelling with higher hydrophilicity at room temperature, which could be used to retrieve tissue constructs. The resulting tissue constructs were the same size as the grooves and could be used as modules in tissue fabrication. Given its ability to form and retrieve cell aggregates and its integration with standard microfabrication, PNIPAAm-coated PDMS templates may become useful for 3D cell culture applications in tissue engineering and drug discovery.     

Surface-induced self-assembly of dipeptides onto nanotextured surfaces

There is an increasing interest for the utilization of biomolecules for fabricating novel nanostructures due to their ability for specific molecular recognition, biocompatibility, and ease of availability. Among these molecules, diphenylalanine (Phe-Phe) dipeptide is considered as one of the simplest molecules that can generate a family of self-assembly based nanostructures. The properties of the substrate surface, on which the self-assembly process of these peptides occurs, play a critical role. Herein, we demonstrated the influence of surface texture and functionality on the self-assembly of Phe-Phe dipeptides using smooth silicon surfaces, anodized aluminum oxide (AAO) membranes, and poly(chloro-p-xylylene) (PPX) films having columnar and helical morphologies. We found that helical PPX films, AAO, and silicon surfaces induce similar self-assembly processes and the surface hydrophobicity has a direct influence for the final dipeptide structure whether being in an aggregated tubular form or creating a thin film that covers the substrate surface. Moreover, the dye staining data indicates that the surface charge properties and hence the mechanism of the self-assembly process are different for tubular structures as opposed to the peptidic film. We believe that our results may contribute to the control of surface-induced self-assembly of peptide molecules and this control can potentially allow the fabrication of novel peptide based materials with desired morphologies and unique functionalities for different technological applications.