Penetration and release studies of positively and negatively charged nanoemulsions--is there a benefit of the positive charge?

The surface of all tissues, including the stratum corneum, carries a negative charge. Following that fact it is assumed that a positively charged topical formulation could lead to an enhanced penetration because of an increased interaction with the negative charge of the membrane. The intention of this study is to prove an enhanced penetration of a positively charged nanoemulsion compared to a negatively charged nanoemulsion, both containing prednicarbate.

Improving the ex vivo stability of drug ester compounds in rat and dog serum: inhibition of the specific esterases and implications on their identity.

In drug development, it has been noticed that some drug compounds, especially esters, are unstable in serum samples ex vivo. This can lead to a substantial underestimation of the actual drug concentration. The rat and the dog, representing a rodent and non-rodent species, respectively, are widely used in preclinical studies.

Development of a positively charged prednicarbate nanoemulsion.

A physically and chemically stable positively charged prednicarbate nanoemulsion was developed as a carrier system for the treatment of atopic dermatitis. Phytosphingosine was used to obtain the positive charge and also because of its supportive properties for the restoration of damaged skin. As production method high pressure homogenization was employed.

Poly(I:C) coated PLGA microparticles induce dendritic cell maturation.

Microparticles from poly(D,L-lactic-co-glycolic acid) [PLGA] are of steadily rising interest for the delivery of antigens to immune cells and the induction of a long-lasting immune response for vaccination or immunological tumor therapy. However, if the desired vaccine contains only weak antigens and fails to activate the antigen presenting cells (APC), the opposite effect, i.e.

Corneal permeation studies of everolimus microemulsion.

Purpose: To prevent corneal-graft rejection, the topical application of an immunosuppressive drug is an alternative to the systemic application of immunosuppressive drugs or corticosteroids, which may have adverse side effects. The aim of this study was to determine the permeation rate of everolimus through freshly isolated pig cornea (ex vivo).

Methods: A fluorescence polarization immunoassay with a commercially available assay system was used to quantify everolimus in the acceptor samples of the permeation tests.

Determination of rat serum esterase activities by an HPLC method using S-acetylthiocholine iodide and p-nitrophenyl acetate.

Establishing esterase assays allows the determination and comparison of esteratic activities of tissues of one organism and between organisms. We have developed a high-performance liquid chromatography (HPLC) assay for the determination of S-acetylthiocholine (ATC) and p-nitrophenyl acetate (NPA) hydrolyzing activities of rat serum esterases based on ion pair chromatography with on-line radiochemical and ultraviolet (UV) detection. ATC is a substrate for cholinesterases, whereas NPA is cleaved by a variety of esterases and other proteins (e.

Changes of the properties in the upper layers of human skin on treatment with models of different pharmaceutical formulations - an ex vivo ESR imaging study.

The noninvasive method of spectral-spatial electron spin resonance imaging (ESRI) was used to obtain a polarity map of human skin. The spin probes TEMPO, TEMPOL, and CAT-1, which are considered to act as drug representatives, were applied as reporter molecules. The polarity in skin layers was described by means of the changes of the hyperfine splitting constant A(iso), which itself is a reflection of interactions at a molecular level, and the effect of polarity on the spatial distribution of spin probes in skin samples was studied.

Formulation of sirolimus eye drops and corneal permeation studies.

The aim of this study was the development of eye drops with 1 mg/mL sirolimus and the evaluation of the drug's ability to permeate the freshly isolated pig cornea. Cyclodextrin solutions, liposomes, hydrotrope mixtures, poloxamer gels, and a microemulsion were tested for their suitability to dissolve the extremely hydrophobic drug sirolimus (solubility in water 2.6 microg/mL).

ESR imaging investigations of two-phase systems.

The possibilities of electron spin resonance (ESR) and electron spin resonance imaging (ESRI) for investigating the properties of the spin probes TEMPO and TEMPOL in two-phase systems have been examined in the systems water/n-octanol, Miglyol/Miglyol, and Precirol/Miglyol. Phases and regions of the phase boundary could be mapped successfully by means of the isotropic hyperfine coupling constants, and, moreover, the quantification of rotational and lateral diffusion of the spin probes was possible. For the quantitative treatment of the micropolarity, a simplified empirical model was established on the basis of the Nernst distribution and the experimentally determined isotropic hyperfine coupling constants.

Antioxidative treatment inhibits the release of thrombogenic tissue factor from irradiation- and cytokine-induced endothelial cells.

Objectives: The aim of this study was to investigate the effect of the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC) on the ionizing radiation (IR)- and tumor necrosis factor-alpha (TNF-alpha) induced tissue factor (TF) expression and its release from human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs were irradiated with a single dose of either 5 Gy or 10 Gy and stimulated with TNF-alpha (10 ng/mL) in the presence or absence of PDTC and NAC, respectively. Quantitative real-time PCR, ELISA, and TF activity measurements were performed, including TF activity in the supernatant.

Increased sensitivity of chitosan determination by a dye binding method.

Chitosan is a topic of current research in pharmaceutics, medicine, biotechnology, and beyond. This note describes an improved quantification of chitosan using the dye Cibacron Brilliant Red 3B-A. The method is sensitive and of a good reproducibility and linearity in the range of 10-80 microg/mL.

A novel agglutination test for antigen-specific detection of platelet antibodies.

A simple and rapid antigen-specific assay for the identification antibodies to platelets is lacking, yet. Red-dyed polystyrene microbeads were coated with monoclonal antibodies to various platelet glycoprotein complexes, and used for the detection of platelet autoantibodies and alloantibodies. The results were largely identical with those obtained by monoclonal antibody-specific immobilization of platelet antigen assay (MAIPA).

Stable cationic microparticles for enhanced model antigen delivery to dendritic cells.

The objectives of this work were (i) to prepare physically stable cationic microparticles and (ii) to study the impact of the surface properties on microparticle phagocytosis and the phenotype of dendritic cells (DC). Protein loaded biodegradable microparticles from poly(lactic-co-glycolic acid) [PLGA] were produced in a micromixer-based w/o/w solvent evaporation procedure. Anionic particles were obtained by using polyvinyl alcohol (PVA) as stabilizing agent; for cationic surfaces cetyltrimethylammonium bromide (CTAB) and chitosan/PVA or DEAE-dextran/PVA blends were evaluated.

A simple and practical assay for the antigen-specific detection of platelet antibodies.

Background: The antigen-specific assays currently used for characterization of platelet (PLT)-reactive auto- and alloantibodies are too technically complex and impracticable for most routine laboratories. Here, a novel antigen-specific particle assay (ASPA) for PLTs similar to that of red blood cells is described.

Study Design And Methods: PLTs were solubilized and then incubated with red-dyed polystyrene particles coated with monoclonal antibodies (MoAbs) to various PLT glycoprotein complexes.

Microenvironmental pH and microviscosity inside pH-controlled matrix tablets: an EPR imaging study.

Incorporation of pH modifiers is a commonly used strategy to enhance the dissolution rate of weakly basic drugs from sustained release solid dosage forms. Electron paramagnetic resonance imaging (EPRI) was applied to spatially monitor pH(M) and the rotational correlation time (tau(R)), a parameter which is closely related to the surrounding microviscosity inside HPMC (hydroxypropylmethylcellulose) matrix tablets. Fumaric, citric, and succinic acid were employed as pH modifiers.

Effect of lipid-containing, positively charged nanoemulsions on skin hydration, elasticity and erythema--an in vivo study.

Dry skin and other skin disorders such as atopic dermatitis are characterized by impaired stratum corneum (SC) barrier function and by an increase in transepidermal water loss (TEWL) leading to a decrease in skin hydration. The possibility that dermatological and cosmetic products containing SC lipids could play a part in the restoration of disturbed skin barrier function is of great interest in the field of dermatology and cosmetics. The aim of the present study was to evaluate the effect of positively charged oil/water nanoemulsions (PN) containing ceramide 3B and naturally found SC lipids (PNSC) such as ceramide 3, cholesterol, and palmitic acid on skin hydration, elasticity, and erythema.

Preparation of protein loaded poly(D,L-lactide-co-glycolide) microparticles for the antigen delivery to dendritic cells using a static micromixer.

The cellular immune response against tumors, viruses, or intracellular bacteria requires adequate antigen delivery to professional phagocytes, their processing and the presentation of antigenic peptides to T-cells. Biodegradable microparticles to enhance antigen phagocytosis and the response of cytotoxic lymphocytes have been proposed. The aim of the present study was to formulate poly(lactide-co-glycolide) (PLGA) microparticles using a w/o/w solvent evaporation procedure in order to obtain suitable vehicles for vaccination.

Design of a phytosphingosine-containing, positively-charged nanoemulsion as a colloidal carrier system for dermal application of ceramides.

Positively charged oil/water (o/w) nanoemulsions (PN) are effective vehicles to change the permeability of the skin. This study focused on the preparation and characterisation of phytosphingosine (PS) containing PN (PPN) which serve as colloidal carriers for the dermal application of ceramide IIIB (CIIIB) and the stratum corneum (SC) lipids (PPNSC) such as ceramide III (CIII), cholesterol, and palmitic acid. The investigations were conducted using appropriate emulsification and homogenisation processing conditions to optimise PPNSC with regard to droplet size, physical stability, and solubility of PS, CIII and CIIIB.

In vivo ESR studies on subcutaneously injected multilamellar liposomes in living mice.

Purpose: An innovative, noninvasive, low-frequency electron spin resonance (ESR) spectroscopy method was applied and adapted to investigate the integrity of multilamellar liposomes from hydrogenated phospholipids after subcutaneous injection in living mice. Moreover, the fate of the injected liposomal preparations was examined, as well as the possibility to achieve a depot effect.

Methods: Highly concentrated solutions of the spin probe 2,2,6,6-tetramethyl-4-trimethylammoniumpiperidine-1-oxyl-iodide (CAT-1; 138 mM) were encapsulated in liposomes.