Investigation of the penetration behaviour of mycophenolate mofetil from a semisolid formulation into human skin ex-vivo.

Mycophenolate mofetil, the morpholinoethylester of mycophenolic acid, is an immunosuppressant used in combination with ciclosporin (cyclosporin) and corticosteroids to prevent organ rejection after heart and kidney transplantations. The drug seems also to be effective in dermal diseases after systemic administration. However, up to date mycophenolate mofetil can be only systemically administered and this is associated with several side effects such as nausea, leucopenia, sepsis, and diarrhoea.

The effect of a functional group in penicillin derivatives on the interaction with bile salt micelles studied by micellar electrokinetic chromatography.

A capillary electrophoresis method is developed and validated for the characterization of the affinity and the interaction between aminopenicillanic acid (APS-H) and its derivatives with bile salt micelles. The micellar systems studied contained sodium taurocholate (NaTC) and sodium deoxycholate (NaDC). Using the retention factor k', functional group selectivity, gammaG, is defined as the ratio of the retention factor of a substituted aminopenicillanic acid (APS-R) over the capacity factor of APS-H and the difference in free energy (deltadeltaG degrees) can be used for the characterization of the affinity and interaction between drugs and micelles.

Characterization of micellar solubilization of antibiotics using micellar electrokinetic chromatography.

Micellar electrokinetic chromatography (nMEKC) method was applied to the determination of the partition behaviour between water and micelle for a group of antibiotics using sodium dodecyl sulphate (SDS) as an anionic model surfactant. In the method, the running buffer contains both the micelles and the drug, and the injected solution contains the same concentration of the micelles as the running buffer but no drug. The mobility of the drug can be measured from a negative peak recorded in the chromatogram.

Homo-phytochelatins are synthesized in response to cadmium in azuki beans.

In a recent report, it was claimed that azuki beans (Vigna angularis) do not synthesize phytochelatins (PCs) upon exposure to cadmium, although glutathione (GSH), the substrate for PC synthesis, is present in this plant. This legume species thus would be the first exception in the plant kingdom that would fail to complex heavy metals by PCs. Here, we report that not GSH, but only homoglutathione can be detected in this plant and that homo-phytochelatins are formed when azuki beans are challenged with heavy metals such as cadmium.

Quantification of mycophenolate mofetil in human skin extracts using high-performance liquid chromatography-electrospray mass spectrometry.

A sensitive and selective method for the quantification of mycophenolate mofetil and its active metabolite mycophenolic acid in different human skin layers after dermal administration is presented. The skin layers were separated after in vitro penetration experiments and a methanolic extraction was performed. Positive ion electrospray HPLC-MS in selected ion monitoring mode was used to quantify the substances after isocratic separation by a C18 analytical column.

Bioadhesion of supramolecular structures at supported planar bilayers as studied by the quartz crystal microbalance.

A quartz crystal microbalance (QCM) was used to study the adhesion behavior of supramolecular aggregates at supported planar bilayers (SPBs). The QCM technique is a suitable method to detect the adsorption of biomolecules at the quartz surface owing to its sensitivity for changes in mass and viscoelastic properties. To simulate biomembranes, the quartz plates were coated with highly ordered lipid films.

The examination of skin lipid model systems stressed by ultraviolet irradiation in the presence of transition metal ions.

In this study, we investigated the effects of ultraviolet (UV) radiation on lipid peroxidation in the presence of ionised iron as a transition metal. Fatty acids as important intercellular stratum corneum lipids and liposomes were used to model skin lipid systems for our experiments. A UV-A laser and a broad spectrum UV lamp were used to create high-level radiation.

Noninvasive characterization of human stratum corneum of undiseased skin of patients with atopic dermatitis and psoriasis as studied by Fourier transform Raman spectroscopy.

Etiopathogenetic regulatory disorders of epidermal metabolism and the subsequent changes in the molecular pattern of the stratum corneum play an important role in the clinical differentiation of particular dermatoses (e.g., psoriasis, atopic dermatitis).

Non-ionic micellar affinity capillary electrophoresis for analysis of interactions between micelles and drugs.

Micellar affinity capillary electrophoresis (MACE) was introduced to evaluate the affinity of various kinds of drugs as benzoic acid, salicylic acid, trinitrophenol, p-hydroxybenzoic acid and o-acetylsalicylic acid. Non-ionic micelles as Brij 35 (polyethylenglycol dodecylether), Tagat (polyoxyethylene (20) glycerol monooleate) and Tween 20 (polyoxyethylen sorbitan monolaurate) were used as a pseudostationary phase in capillary electrophoresis. For polyvinyl alcohol (PVA) coated capillary was used in this examinations.

[Morphological evaluation of posterior capsule opacification in diffractive multifocal intraocular lenses].

Background: Diffractive multifocals belong to the first generation of multifocal intraocular lenses. Dure to their optical principle of diffraction multifocals separate the incoming light on two foci (41%) with 18% loss of scattered light. Therefore, reduced contrast sensitivity and glare have been frequently described with this lens.

Penetration of compounds through human stratum corneum as studied by Fourier transform infrared photoacoustic spectroscopy.

The penetration of the lipophilic model permeant, 1-cyanodecane, into isolated human stratum corneum (SC) was followed nondestructively by step-scan Fourier transform infrared (FTIR) photoacoustic spectroscopy (PAS) with phase modulation technique. The uptake of the compound in the SC was quantified by monitoring the alterations in the spectra in the course of the penetration using multivariate analysis. Step-scan technique in conjunction with phase modulation offers the possibility for controllable depth profiling (sampling depth up to 30 microm) during the penetration process.

X-ray diffraction and spectroscopic studies of oleic acid-sodium oleate.

The sodium oleate-oleic acid (1:1) complex (NaHOl(2)) is characterized using X-ray diffraction, FT-IR photoacoustic spectroscopy, FT-Raman spectroscopy, and DSC. The special arrangement of hydrogen-bonded pairs of carboxylic acid and carboxylate groups into unique "head-group" is supported by frequency shifts and partial or total disappearance of characteristic vibrations of carboxylic acid dimer and of carboxylate groups. The well-ordered state of hydrocarbon chains is demonstrated by the existence of sharp Raman bands in the C-C stretching region (1000-1150 cm-1) and other conformationally sensitive modes.

Investigation of drug release from suspension using FTIR-ATR technique: part II. Determination of dissolution coefficient of drugs.

Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy was applied to a release experiment in order to determine the dissolution coefficient of drug particles in heterogeneous semisolid formulations. The drug release experiment was carried out using ketoconazole suspended in Vaseline with various amounts of paraffinum liquidum as donor and an artificial dodecanol-collodion (DDC) membrane as acceptor compartment. Monitoring changes in IR bands due to ketoconazole the decrease of the drug content near the ATR crystal ointment was followed as a function of time.

Drug penetration as studied by noninvasive methods: fourier transform infrared-attenuated total reflection, fourier transform infrared, and ultraviolet photoacoustic spectroscopy.

The penetration of the drugs dithranol and methoxsalen from semisolid Vaseline formulation into an artificial dodecanol-collodion membrane was followed by three spectroscopic methods; they are, step-scan Fourier transform infrared (FTIR) photoacoustic spectroscopy (PAS) with phase modulation, FTIR-attenuated total reflection (FTIR-ATR), and ultraviolet (UV) PAS. The uptake of the drug in the membrane was quantified by monitoring the dependence of an appropriate drug band on the penetration time. The PAS experiments were carried out with various modulation frequencies for generating various sampling depths.

Assessing lymphocyte functions in neonates for revealing abnormal prenatal development of the immune system.

Because it is difficult to assess prenatally induced functional deficits of the human immune system, we developed an ex vivo method for differentiation and maturation of peripheral lymphocytes of newborn, preferentially using umbilical cord blood. Many lymphocyte subsets of newborn infants are "immature" with respect to defined surface receptors. An example of such an immaturity is the almost complete lack of "memory"-type helper T cells (also designated as helper-inducer cells), characterized by expressing the surface receptors: CD4(+)CD45R0(+)CD45RA(-)CD29(high).

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system: 3. Plasma immunoglobulins and cytokines of workers with quantified moderately-increased body burdens.

The concentrations of immunoglobulins (IgA, IgD, IgG, IgM) and of several cytokines were measured in the plasma of volunteers with clearly, but moderately, increased body burdens of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), using monoclonal antibodies and an enzyme-linked immuno-sorbant assay. Two groups of workers with different body burdens of PCDD/PCDF were studied: (trial I) persons with mainly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and (trial II) persons with mainly penta- and hexachlorinated dibenzofurans (P5CDF/H6CDF) in their blood fat. Including the reference group, 158 volunteers were investigated.

Ceramide analysis utilizing gas chromatography-mass spectrometry.

Suitable analytical methods are a prerequisite of a detailed investigation of ceramides. Therefore, a new gas chromatograph-mass spectrometry method with electron impact ionization was developed. Samples have been prepared for gas chromatography by the formation of volatile trimethylsilyl derivatives.

Characterization of partition and thermodynamic properties of cephalosporins using micellar electrokinetic chromatography in glycodeoxycholic acid solution.

Micellar electrokinetic chromatography (MEKC) was introduced to evaluate the hydrophobicity of cephalosporins (cefpim, cefpirom, cefazolin, ceftazidim, cephradin, cefuroxim, cefotaxim, cephapirin and cephalothin). Partition coefficients of cephalosporins were calculated between a micelle and an aqueous phases from the measurement of the migration time, provided the critical micelle concentration and the phase ratio are known. Thermodynamic quantities such as enthalpy and entropy changes of micellar solubilization were calculated from the temperature dependence on the partition coefficients.

Capillary zone electrophoresis determination of meropenem in biological media using a high sensitivity cell.

A capillary electrophoresis method with a high sensitivity cell (Z-cell) has been developed for the determination of meropenem in aqueous solution and in biological media (urine, plasma). Water samples were analysed using two calibration curves of meropenem with standard capillary and a capillary with a high sensitivity cell. In urine, the samples were only diluted in buffer and were injected without any further sample preparation.

Characterization of cephalosporin transfer between aqueous and colloidal phases by micellar electrokinetic chromatography.

A new electrokinetic chromatographic method was applied to the determination of the partition coefficient between water and micelle for a group of cephalosporins (cefmetazol, cephradin, cefaclor, ceftazidim, cefodizim, cephapirin, cephalothin and ceftriaxon) using sodium dodecyl sulphate as an anionic surfactant in microemulsion and in micellar systems. In the new method, the running buffer contains both the micelles and the drug, and the injected solution contains the same concentration of micelles as the running buffer but not the drug. The mobility of the drug can be measured from a negative peak recorded the chromatogram.

Thiamine analysis in biological media by capillary zone electrophoresis with a high-sensitivity cell.

A capillary zone electrophoresis method with high-sensitivity cell (Z-cell) has been developed for the determination of thiamine in biological media (plasma, urine, saliva). The urine samples were diluted (1:1, v/v) in water and were directly injected into the apparatus. For the quantitative assay of thiamine in plasma it is necessary to precipitate the protein component.

Quantification of hyaluronan in pharmaceutical formulations using high performance capillary electrophoresis and the modified uronic acid carbazole reaction.

The amount of hyaluronan (HA) in pharmaceutical formulations was determined by high-performance capillary electrophoresis (HPCE) and the results were compared with the carbazole reaction established by Bitter and Muir (T. Bitter, H.M.

Interactions between food components and drugs. Part 8: Effect of pectins and bile acid preparations forming stable mixed micelles on transport of quinine in vitro.

Interactions between quinine and acetylated pectin, amidated pectin and pectin with blockwise arrangement of the free carboxyl groups as well as interactions between quinine and bile salt preparations forming stable mixed bicelles have been investigated. A diffusion cell with two compartments and an artificial lipid membrane and a filter-grown colon carcinoma cell line (Caco-2) have been used. Depending on structural parameters, pectin preparations diminished the rate of permeation of the drug.