Drug Release from ß-Cyclodextrin Complexes and Drug Transfer into Model Membranes Studied by Affinity Capillary Electrophoresis.

Purpose: Is to characterize the drug release from the ß-cyclodextrin (ß-CD) cavity and the drug transfer into model membranes by affinity capillary electrophoresis. Phospholipid liposomes with and without cholesterol were used to mimic the natural biological membrane.

Methods: The interaction of cationic and anionic drugs with ß-CD and the interaction of the drugs with liposomes were detected separately by measuring the drug mobility in ß-CD containing buffer and liposome containing buffer; respectively.

Synthesis and characterization of novel 1,2,4-triazine derivatives with antiproliferative activity.

A series of novel small molecules with a 1,2,4-triazine scaffold was obtained according to a recently published and highly efficient synthetic route. Screening for antiproliferative and cytotoxic activity revealed distinct anticancer effects against the human leukemia cell line K-562 combined with a remarkable low cytotoxicity. All compounds were in agreement with the 'rule-of-five' claims by Lipinski and calculated logP(calc) values were experimentally confirmed (logP(exp)).

Heterobifunctional isotope-labeled amine-reactive photo-cross-linker for structural investigation of proteins by matrix-assisted laser desorption/ionization tandem time-of-flight and electrospray ionization LTQ-Orbitrap mass spectrometry.

Chemical cross-linking combined with a subsequent enzymatic digestion and mass spectrometric analysis of the created cross-linked products presents an alternative approach to assess low-resolution protein structures. By covalently connecting pairs of functional groups within a protein or a protein complex a set of structurally defined interactions is built up. We synthesized the heterobifunctional amine-reactive photo-cross-linker N-succinimidyl p-benzoyldihydrocinnamate as a non-deuterated (SBC) and doubly deuterated derivative (SBDC).

Penetration profile of taurine in the human skin and its distribution in skin layers.

Purpose: To measure in vitro release of taurine from a semisolid standard formulation (amphiphilic cream, DAC) containing 1% taurine, a multi-layer membrane system was used. The content and distribution of taurine in different healthy skin layers (stratum corneum, epidermis and dermis) before (native taurine) and after application of the DAC cream were determined using capillary electrophoresis.

Methods: The release of taurine from the DAC cream was studied using a multilayer membrane system.

Development of capillary electrophoresis methods for quantitative determination of taurine in vehicle system and biological media.

CE methods have been developed for the determination of taurine in pharmaceutical formulation (microemulsion) and in biological media such as sweat. The CE system with end-column pulsed amperometric detection has been found to be an interesting method in comparison with UV and fluorescence detection for its simplicity and rapidity. A gold-disk electrode of 100 mm diameter was used as the working electrode.

Antioxidant and photoprotective properties of an extract from buckwheat herb (Fagopyrum esculentum MOENCH).

In recent years, the incidence of skin cancer has risen remarkably. Sun light, especially the included ultraviolet (UV)-radiation, is seen as important trigger for the development of skin cancer. Thus, there is an increasing interest in the development of UV-protective substances to use them as sun care products.

The detection of UV-induced membrane damages by a combination of two biosensor techniques.

Ketoprofen is an important anti-inflammatory drug, but its dermal application is limited because of the photosensitizing properties causing phototoxic reactions of the skin when exposed to UV light. We have recently investigated the peroxide formation of ketoprofen in solutions of linoleic acid during UV irradiation. To continue these studies and focus on UV-induced changes in membrane integrity and barrier function we established an in vitro model using two biosensor techniques simultaneously.

Identification of hyaluronic acid oligosaccharides by direct coupling of capillary electrophoresis with electrospray ion trap mass spectrometry.

A new method for the identification of oligosaccharides obtained by enzymatic digestion of hyaluronic acid (HA) with bacterial hyaluronidase (HA lyase, E.C. 4.

Capillary zone electrophoresis with electrochemical detection--a simple and effective method to analyze oxygen-consuming and peroxide-forming processes.

Numerous biological, chemical and photochemical processes consume molecular oxygen, thereby forming peroxides, hydroperoxides and even hydrogen peroxide. This paper describes a new system for monitoring quasi simultaneously oxygen uptake and peroxide formation. For this purpose capillary electrophoresis with electrochemical detection was connected to a new automated injector that periodically injects a sample of the reaction mixture into the capillary electrophoresis system without any contact with the atmosphere.

Pulsed amperometric detection of calystegines separated by capillary electrophoresis.

Calystegines are polyhydroxyalkaloids with a nortropane skeleton. They are oxidized by pulsed amperometry at a gold electrode due to their vicinal hydroxyl groups similar to monosaccharides, but at a slightly higher potential. Compared to carbohydrates, calystegines exhibit lower acidity, thus the effective electrophoretic mobility as anions in 0.

UV-induces formation of hydrogen peroxide based on the photochemistry of ketoprofen.

Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug. However, application to the skin is problematic because the photosensitizing properties of the benzophenone moiety may cause phototoxic effects when the treated skin region is exposed to UVA light. Using capillary electrophoresis with electrochemical detection we are able to differentiate the peroxides formed during illumination of KP-containing solutions of linoleic acid.

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.

Determination of peroxides by capillary zone electrophoresis with amperometric detection.

The combination of cathodic amperometric detection with capillary zone electrophoresis is demonstrated to be a versatile method for the quantification of organic and inorganic peroxides. A gold microelectrode, polarized at -600 mV against an Ag/AgCl reference electrode, is placed at the end of the capillary. Since the electroosmotic flow purges the detector electrode from oxygen, no degassing of the detector cell or the sample is necessary.

Characterization of partitioning behavior of cephalosporins using microemulsion and micellar electrokinetic chromatography.

Electrokinetic chromatography (EKC) was introduced to determine the partitioning behavior of various cephalosporins (cefpim, cefpirom, cefaloridin, cefaclor, cephalexin, cefuroxim, cefotaxim) in microemulsions (ME) and micellar (MC) systems. The partitioning behavior of cephalosporins in microemulsions was characterized calculating the capacity factor. The required parameters for the determination of the capacity factor (micro(aq) and micro-me are the electrophoretic mobilities of the solutes in the aqueous phase and the microemulsion phase, micro(eff) is the effective mobility in the microemulsion solution) were measured by EKC using cationic and anionic microemulsion systems consisting of the surfactants/n-heptane/1-butanol/10 mM phosphate buffer solution, pH 7.

Characterization of interaction between cephalosporins and charged surfactants using capillary zone electrophoresis.

Capillary electrophoresis offers a new way of characterizing the interaction between surfactants and drugs. This interaction was studied using capillary zone electrophoresis (CZE). It was observed that addition of tetraalkylammonium bromide to the electrolyte buffer at different concentrations of dodecyl trimethylammonium bromide (DTAB) led to a change of the migration time (tm) and of the ionic mobility (mu) of cephalosporins.

Application of capillary electrophoresis of characterizing interactions between drugs and bile salts. Part I.

Capillary electrophoresis offers a new way of characterizing interactions between different bile salts and drugs. The observed interactions were characterized with modified model functions known from affinity capillary electrophoresis (ACE) an micellar electrokinetic capillary electrophoresis (MECC). The methodical background of both methods is the change of the ionic mobility of the drug caused by partition between phases and aggregation with the bile salt molecules, respectively.

Treatment of multiple sclerosis with 15 +/- deoxyspergualin. Design of a controlled study with close MRI-monitoring.

The rationale and design of a prospective randomized double blind study of 15 +/- Deoxyspergualin in the treatment of Multiple Sclerosis are presented. The study was started in autumn 1992 and will include more than 200 patients who will be randomized either to DSG low dose or DSG high dose or placebo. Average number of contrast enhancing lesions in monthly cranial MRIs during the first six months of treatment and change in EDSS at the end of the two-year study period will be the main efficacy parameters.

Intrathecal versus systemic corticosteroids in the treatment of multiple sclerosis: results of a pilot study.

Fifty patients with multiple sclerosis were treated either by corticosteroids given systemically or by intrathecal injection of a steroid crystal suspension. Before and 3 weeks after the beginning of the treatment we examined the patients according to the Expanded Disability Status Scale (EDSS). Four patients had to be excluded from evaluation.

A trial of dipyridamole and aspirin in the prevention of smoking-induced changes in platelets and endothelium in men with coronary artery disease.

A random-order, double-blind crossover study compared the effects of placebo, dipyridamole and dipyridamole plus aspirin on smoking-induced changes in endothelium and platelets. Each of 12 male habitual smokers with coronary artery disease was given dipyridamole (75 mg) and aspirin (324 mg), dipyridamole (75 mg) and placebo for aspirin, or a placebo for each drug 3 times daily for 1 week before each of three 20-minute periods (separated by 2 weeks) of smoking 2 cigarettes after a 12-hour period of abstinence. During each period of smoking there were increases in the mean values of the plasma concentrations of beta-thromboglobulin, platelet factor 4 and nicotine, the endothelial cell count and the blood level of carboxyhemoglobin.