Modelling antibiotic and cytotoxic isoquinoline effects in Staphylococcus aureus, Staphylococcus epidermidis and mammalian cells.

Isoquinolines (IQs) are natural substances with an antibiotic potential we aim to optimize. Specifically, IQ-238 is a synthetic analog of the novel-type N,C-coupled naphthylisoquinoline (NIQ) alkaloid ancisheynine. Recently, we developed and tested other IQs such as IQ-143.

Fatty acid composition analysis in polysorbate 80 with high performance liquid chromatography coupled to charged aerosol detection.

The fatty acid (FA) composition of polysorbate 80 (PS80), a sorbitan oleic acid ester copolymerized with about 20mole of ethylene oxide, is typically characterized by gas chromatography. Here, an alternative method was developed. After saponification with potassium hydroxide the FA fraction was collected with liquid-liquid extraction using methyl-tert-butyl ether.

Simple and rapid high performance liquid chromatography method for the determination of polidocanol as bulk product and in pharmaceutical polymer matrices using charged aerosol detection.

Currently, neither the European nor the United States Pharmacopoeia provide a method for the determination of polidocanol (PD) content despite the fact that PD, besides being an excipient, is also used as an active pharmaceutical ingredient. We therefore developed a method where the PD content was determined using a Kinetex C18 column operated at 40°C with water-acetonitrile (15:85, v/v) as mobile phase. A Corona(®) charged aerosol detector was employed for the detection of PD that is lacking a suitable UV chromophore.

Protein release from electrospun nonwovens: improving the release characteristics through rational combination of polyester blend matrices with polidocanol.

Nonwoven scaffolds consisting of poly-ε-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) and polidocanol (PD), and loaded with lysozyme crystals were prepared by electrospinning. The composition of the matrix was varied and the effect of PD content in binary mixtures, and of PD and PLGA content in ternary mixtures regarding processability, fiber morphology, water sorption, swelling and drug release was investigated. Binary PCL/PD blend nonwovens showed a PD-dependent increase in swelling of up to 30% and of lysozyme burst release of up to 45% associated with changes of the fiber morphology.

Evaluation of enantiomeric purity of magnesium-L-aspartate dihydrate.

Magnesium supplementation in form of organic magnesium salts is a very popular practice. We examined the enantiomeric purity of "Magnesium aspartate dihydrate" monographed in the European Pharmacopeia. A chiral capillary zone electrophoresis using (2-hydroxypropyl)-β-cyclodextrin coupled to laser induced fluorescence detection and a HPLC-fluorescence method with chiral derivatization using o-phthaldialdehyde and N-acetyl-L-cysteine as an orthogonal method were developed and validated.

Oral drug delivery of therapeutic gases - carbon monoxide release for gastrointestinal diseases.

Deploying the therapeutic potential of carbon monoxide (CO) in various gastrointestinal diseases is challenged by inappropriate oral delivery modes. It is for this challenge, that we developed an easy to use tablet referred to as oral carbon monoxide release system (OCORS) providing precise, controlled, tunable and targeted CO delivery for the treatment of sequelae of gastrointestinal diseases. OCORS is an oral tablet based on sulfite induced CO release from the CO releasing molecule 2 (CORM-2).

Silk fibroin layer-by-layer microcapsules for localized gene delivery.

Herein, we describe the delivery of plasmid DNA (pDNA) using silk fibroin (SF) layer-by-layer assembled microcapsules. Deposition of fluorescently labeled SF onto polystyrene (PS) template particles resulted in increasing fluorescence intensity and decreasing surface charge in correlation to SF layer number. After removal of the PS core, hollow, monodisperse, and structurally stable SF microcapsules of variable size and shell thickness were obtained.

Controlled protein delivery from electrospun non-wovens: novel combination of protein crystals and a biodegradable release matrix.

Poly-ε-caprolactone (PCL) is an excellent polymer for electrospinning and matrix-controlled drug delivery combining optimal processability and good biocompatibility. Electrospinning of proteins has been shown to be challenging via the use of organic solvents, frequently resulting in protein unfolding or aggregation. Encapsulation of protein crystals represents an attractive but largely unexplored alternative to established protein encapsulation techniques because of increased thermodynamic stability and improved solvent resistance of the crystalline state.

Suppression of cytokine release by fluticasone furoate vs. mometasone furoate in human nasal tissue ex-vivo.

Background: Topical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse.

Objective: To compare the activity of two intranasal glucocorticoids, fluticasone furoate (FF) and mometasone furoate (MF) with respect to the inhibition of T helper (Th)1, Th2 and Th17 cytokine release in airway mucosa.

Impurity profiling of carbocisteine by HPLC-CAD, qNMR and UV/vis spectroscopy.

For the impurity profiling of the mucolytic and anti-inflammatory drug carbocisteine a high performance liquid chromatographic (HPLC) method using corona charged aerosol detection (CAD) was developed and fully validated following the ICH guideline Q2(R1). The response was linear (R²>0.995) over a small concentration range (0.

Decoration of silk fibroin by click chemistry for biomedical application.

Silkfibroin (SF) has an excellent biocompatibility and its remarkable structure translates into exciting mechanical properties rendering this biomaterial particularly fascinating for biomedical application. To further boost the material's biological/preclinical impact, SF is decorated with biologics, typically by carbodiimide/N-hydroxysuccinimide coupling (EDC/NHS). For biomedical application, this chemistry challenges the product risk profile due to the formation of covalent aggregates, particularly when decoration is with biologics occurring naturally in humans as these aggregates may prime for autoimmunity.

Insulin-like growth factor-I aerosol formulations for pulmonary delivery.

Injectable insulin-like growth factor-1 (IGF-I) is therapeutically deployed for severe IGF-I deficiency and clinically explored for various other indications such as muscle wasting disease. In the present study, liquid IGF-I formulations for pulmonal application were screened with regard to buffer type (acetate, citrate, histidine, and succinate), sodium chloride concentration (50-150 mM), and pH value (4.5-6.

Silk constructs for delivery of musculoskeletal therapeutics.

Silk fibroin (SF) is a biopolymer with distinguishing features from many other bio- as well as synthetic polymers. From a biomechanical and drug delivery perspective, SF combines remarkable versatility for scaffolding (solid implants, hydrogels, threads, solutions), with advanced mechanical properties and good stabilization and controlled delivery of entrapped protein and small molecule drugs, respectively. It is this combination of mechanical and pharmaceutical features which renders SF so exciting for biomedical applications.

New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities.

Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro).

Bone targeting for the treatment of osteoporosis.

Osteoporosis represents a major public health burden especially considering the aging populations worldwide. Drug targeting will be important to better meet these challenges and direct the full therapeutic potential of therapeutics to their intended site of action. This review has been organized in modules, such that scientists working in the field can easily gain specific insight in the field of bone targeting for the drug class they are interested in.

Design and synthesis of novel 2-amino-5-hydroxyindole derivatives that inhibit human 5-lipoxygenase.

Compounds that inhibit 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of leukotrienes (LTs), possess potential for the treatment of inflammatory and allergic diseases as well as of atherosclerosis and cancer. Here we present the design and the synthesis of a series of novel 2-amino-5-hydroxyindoles that potently inhibit isolated human recombinant 5-LO as well as 5-LO in polymorphonuclear leukocytes, exemplified by ethyl 2-[(3-chlorophenyl)amino]-5-hydroxy-1H-indole-3-carboxylate (3n, IC(50) value congruent with 300 nM). Introduction of an aryl/arylethylamino group or 4-arylpiperazin-1-yl residues into position 2 of the 5-hydroxyindoles was essential for biological activity.

(S)-Thiirancarboxylic acid as a reactive building block for a new class of cysteine protease inhibitors.

For (S)-thiirancarboxylic acid a second-order rate constant of k2nd = 222 M(-1) min(-1) for the irreversible inhibition of papain was determined. The ethyl and methyl ester do not inhibit the enzyme time-dependently. An improved synthesis of enantiomerically pure thiirancarboxylic acid is described.

Simultaneous quantification of released succinic acid and a weakly basic drug compound in dissolution media.

A HPLC-method was developed to determine both fenoldopam, a weakly basic drug and succinic acid, a pH-adjuster for this drug in dissolution media. The usual assays for succinic acid were not applicable due to its low UV-absorption, the low pH-value of samples or the presence of buffer salts and fenoldopam. The described method is a simple non-ion-pair reversed phase HPLC-method using a fast scanning UV-detector and a PC software program for the quantification of both components.