Biomedical subjects

Rainer H Müller

Publications and source records attributed to Rainer H Müller.

30 records · Page 2Linked to original sources

PubMed2003

Functional groups on polystyrene model nanoparticles: influence on protein adsorption.

The surface characteristics of intravenously administered particulate drug carriers decisively influence the protein adsorption that is regarded as a key factor for the in vivo fate of the carriers. Latex nanoparticles were synthesized to study the influence of different basic and acidic functional groups on particulate surfaces on the protein adsorption from human serum. The protein mass adsorbed to the particles was assessed by BCA protein assay, the protein adsorption patterns were analyzed by two-dimensional electrophoresis. Considerable differences in the protein adsorption with regard to preferential adsorbed proteins were detectable for the different functional groups. Possible correlations between the surface characteristics and the protein adsorption are shown and discussed. The knowledge concerning the interactions of proteins and nanoparticles can be used for a rational development of particulate drug carriers and can also be useful for an optimized design of medical devices, e.g., hemodialysis membranes or implants.

Adsorption↗

PubMed2003

Plasma protein adsorption patterns on surfaces of Amphotericin B-containing fat emulsions.

Nephrotoxicity of the conventional Amphotericin B formulation Fungizone is the most common side effect in treatment of systemic fungal infections. Lipid formulations of Amphotericin B including fat emulsions showed a reduced nephrotoxicity. In vivo distribution studies of lipid formulations have shown an accumulation of Amphotericin B in liver and spleen, while concentration in the kidneys is reduced. Blood proteins adsorbed onto particles after intravenous administration are regarded as the key factors determining their in vivo fate. Two-dimensional polyacrylamid gel electrophoresis is a powerful tool for analysis of protein adsorption patterns. This paper deals with the question if there is any correlation between proteins adsorbed on surfaces of AmB fat emulsions produced with a new production technique and the potentially organ distribution of this formulation.

Adsorption↗

PubMed2003

Cosmetic applications for solid lipid nanoparticles (SLN).

Solid lipid nanoparticles (SLN) are novel delivery systems for pharmaceutical and cosmetic active ingredients. This paper highlights advantages of SLN for cosmetic applications. The dependence of the occlusive effect on the particle size of SLN due to film formation is presented by in vitro data. An in vivo study showed that addition of 4% SLN to a conventional o/w cream lead to an increase of skin hydration of 31% after 4 weeks. The application of SLN as physical sunscreens and as active carriers for molecular sunscreens has also been investigated. The amount of molecular sunscreen could be decreased by 50% while maintaining the protection level compared to a conventional emulsion.

Administration, Topical↗

PubMed2003

Oligomers of the arginine-rich motif of the HIV-1 TAT protein are capable of transferring plasmid DNA into cells.

We constructed multimers of the TAT-(47-57) peptide. This polycationic peptide is known to be a protein and particle transduction domain and at the same time to comprise a nuclear localization function. Here we show that oligomers of the TAT-(47-57) peptide compact plasmid DNA to nanometric particles and stabilize DNA toward nuclease degradation. At optimized vector compositions, these peptides mediated gene delivery to cells in culture 6-8-fold more efficiently than poly-L-arginine or the mutant TAT(2)-M1. When DNA was precompacted with TAT peptides and polyethyleneimine (PEI), Superfect, or LipofectAMINE was added, transfection efficiency was enhanced up to 390-fold compared with the standard vectors. As early as after 4 h of transfection, reporter gene expression mediated by TAT-containing complexes was higher than the 24-h transfection level achieved with a standard PEI transfection. When cells were cell cycle-arrested by serum starvation or aphidicolin, TAT-mediated transfection was 3-fold more efficient than a standard PEI transfection in proliferating cells. In primary nasal epithelial cells and upon intratracheal instillation in vivo, TAT-containing complexes were superior to standard PEI vectors. These data together with confocal imaging of TAT-DNA complexes in cells support the hypothesis that the TAT nuclear localization sequence function is involved in enhancing gene transfer.

Amino Acid Motifs↗

PubMed2003

The influence of solid lipid nanoparticles on skin hydration and viscoelasticity--in vivo study.

Effects on skin hydration and viscoelasticity are important criteria during the development of novel cosmetic formulations. This study focuses on the in vivo performance of a conventional o/w cream and of the same cream enriched with solid lipid nanoparticles (SLN). Influences on skin hydration and viscoelastic properties were investigated with validated devices (Corneometer and Cutometer). After an application period of 4 weeks, significant changes in skin hydration were detected for both formulations. The SLN-enriched cream was significantly more effective than the conventional cream (+24% for the cream and +31% for the SLN-cream). The viscoelastic parameters UF and UA/UF remained almost unchanged, which is attributed to the young age of the volunteers. At this stage, SLN represent a promising compound for hydrating new cosmetic formulations.

Administration, Topical↗

PubMed2003

Intravenous itraconazole emulsions produced by SolEmuls technology.

Itraconazole is a drug which is poorly soluble in both the water and oil phases of emulsions. Incorporation in parenteral emulsions was performed applying the SolEmuls Technology, i.e. localising the drug in the interfacial lecithin layer of the emulsions by homogenising a hybrid dispersion of oil droplets and drug nanocrystals in water. The maximum loading capacity of the emulsion system was found to be 10 mg/ml; at 20 mg/ml the loading capacity was exceeded leading to remaining drug nanocrystals in the emulsion. Incorporation of itraconazole into the lecithin layer led to an enhanced dispersion effect, i.e. with increasing drug concentration the droplet size of the emulsions decreased. Physical long-term stability of the optimum emulsion with 10 mg/ml could be shown over a period of 3 months at room temperature.

Antifungal Agents↗

PubMed2003

Plasma protein adsorption of Tween 80- and poloxamer 188-stabilized solid lipid nanoparticles.

The plasma proteins adsorbing onto intravenously injected carriers are considered to be crucial factors determining the organ distribution. Plasma protein adsorption patterns were analyzed on solid lipid nanoparticles (SLN) stabilized with Tween 80 or stabilized with poloxamer 188. The binding patterns were determined by applying two different sample preparation methods, i.e. removal of the SLN from the plasma by (a) centrifugation and (b) gel filtration to assess, if the separation method has an effect on the patterns obtained. The Tween 80-modified SLN adsorbed the major plasma proteins known from particles with blood-brain barrier specificity. Poloxamer 188-surface modified SLN adsorbed the proteins known from model particles that exhibit prolonged circulation time in the blood. It is concluded that the biodegradable SLN stabilized with Tween 80 can potentially be used as drug carriers to the blood-brain barrier having a relatively long residence time in the blood stream. For the poloxamer 188-stabilized SLN a relatively long resistance time in the blood is predicted leading to potential accumulation in the bone marrow when looking at the distinct CII/CIII adsorption.

Adsorption↗

PubMed2002

Lipase degradation of Dynasan 114 and 116 solid lipid nanoparticles (SLN)--effect of surfactants, storage time and crystallinity.

In vivo drug release from solid lipid nanoparticles (SLN) takes place by diffusion and degradation of the lipid matrix. SLN with different degree of crystallinity were prepared to study the effect of crystallinity on the degradation velocity. These SLN were produced by using glycerides with different length of fatty acid chains and known differences in crystallisation velocity (Dynasan 114 and 116), and using stabilisers interfering differently with the crystallisation process of the lipid matrix (cholic acid sodium salt (NaCh), Poloxamer 407 (Plx 407)). NaCh disturbs the crystallisation process, Poloxamer shows little interference. The particles were characterised by photon correlation spectroscopy (PCS) and differential scanning calorimetry (DSC), degradation velocity was determined directly after production and during storage up to 4 weeks under different storage conditions using an especially developed assay based on the NEFA Test kit. After production, SLN with a lower crystallinity matrix (Dynasan 114 and 116, NaCh) degraded faster than higher crystalline particles (all SLN with Plx 407), and showed a decrease in degradation velocity with increasing crystallinity during storage. Fast crystallising particles made from Dynasan 116 stabilised with the non-interfering Plx 407 showed no change in the degradation velocity during storage. SLN produced with a higher crystalline lipid in combination with the crystallisation-disturbing NaCh (Dynasan 116, NaCh) required a 'ripening time' to reach sufficient crystallinity.

Chemistry, Pharmaceutical↗

PubMed2002

Transdermal delivery of highly lipophilic drugs: in vitro fluxes of antiestrogens, permeation enhancers, and solvents from liquid formulations.

PURPOSE: Highly lipophilic basic drugs, the antiestrogens AE 1 (log P = 5.82) and AE 2 (log P = 7.8) shall be delivered transdermally. METHODS: Transdermal permeation of drugs, enhancers, and solvents from various fluid formulations were characterized by in-vitro permeation studies through excised skin of hairless mice. Furthermore, differential scanning calorimetry (DSC) measurements of skin lipid phase transition temperatures were conducted. RESULTS: Transdermal flux of highly lipophilic drugs was extraordinarily enhanced by the unique permeation enhancer combination propylene glycol-lauric acid (9 + 1): steady-state fluxes of AE 1 and AE 2 were as high as 5.8 microg x cm(-2) x h(-1) and 3.2 microg x cm(-2) x h(-1), respectively. This dual enhancer formulation also resulted in a marked increase in the transdermal fluxes of the enhancers. Furthermore, skin lipid phase transition temperatures were significantly reduced by treatment with this formulation. CONCLUSION: Transdermal delivery of highly lipophilic drugs can be realized by using the permeation enhancer combination propylene glycol-lauric acid. The extraordinary permeation enhancement for highly lipophilic drugs by this formulation is due to mutual permeation enhancement of these two enhancers and their synergistic lipid-fluidising activity in the stratum corneum.

Adjuvants, Pharmaceutic↗

PubMed2002

A novel formulation for superparamagnetic iron oxide (SPIO) particles enhancing MR lymphography: comparison of physicochemical properties and the in vivo behaviour.

The major aim of this study was to prove or disprove the theories concerning the correlation between physicochemical properties of superparamagnetic iron oxide (SPIO) particles and their accumulation in the lymph nodes. New SPIO particles were produced using starch as stabilising polymer shell. The synthesis was done in a two-step procedure using conventional wet-chemical precipitation technique and subsequent coating of the iron oxide cores. The particles were physicochemically characterised and their lymphotrophy studied in rats using well described lymphotropic dextran-coated SPIO particles as reference. Despite the short blood half-lives of approximately 13 min and the relatively large sizes (approximately 60-90 nm), the starch SPIO particles proved at least as efficient in lymph node accumulation as the small 25 nm dextran SPIO particles having a half-life of 90 min. The currently accepted theories concerning the connection between particle properties and their uptake into lymph nodes are not generally valid, or have at least to be limited for dextran-coated SPIO particles. Lymph node targeting could be achieved despite the present theories consider small size (<30 nm) and long circulation times in the blood as prerequisites. Histological examination showed, that SPIO particles could only be found in lymph node areas where macrophages could be marked which enclosed the particles. Localisation in marginal areas of the lymph nodes indicates endothelial transcytosis as the major accumulation pathway.

Animals↗

PubMedDate not supplied

Characterization of nebulized buparvaquone nanosuspensions--effect of nebulization technology.

The poorly soluble drug buparvaquone is proposed as an alternative treatment of Pneumocystis carinii pneumonia (PCP) lung infections. Physically stable nanosuspensions were formulated in order to deliver the drug at the site of infection using nebulization. The aerosolization characteristics of two buparvaquone nanosuspensions were determined with commercial jet and ultrasonic nebulizer devices. Aerosol droplet size distribution was determined with laser diffractometry (LD). Nebulization of the nanosuspensions and dispersion media surfactant solutions produced aerosol droplets diameters in the range from 3 to 5 microm for Respi-jet Kendall, Pari Turbo Boy system and Multisonic nebulizers and particles around 9-10 microm with Omron U1. Fractions of the nanosuspensions from the nebulizer reservoir and of aerosol produced were collected to investigate changes in the size of the drug nanocrystals influenced by the nebulization technology. Comparisons were performed measuring the drug nanocrystals with photon correlation spectroscopy (PCS) and LD of the samples. Drug particle aggregates were detected in the fractions of aerosol collected from jet nebulizers. Nebulizer technology (jet vs. ultrasonic) showed influence on the stability of the drug particle size distribution of buparvaquone nanocrystals during the nebulization time evaluated.

Lasers↗

PubMedDate not supplied

New method for the effective production of ultrafine drug nanocrystals.

Particle size reduction, particularly nanonization, is a non-specific, universal approach to improve the bioavailability of poorly soluble drugs. The decreased particle size of drug nanocrystals leads to a distinct increase in surface area. Due to the increased surface area the rate of dissolution will be proportionally raised, leading to a better absorption of the poorly soluble drug. Various technologies for the production of drug nanocrystals are known, e.g., pearl milling (Nanocrystal technology, elan/Nanosystems), high pressure homogenization in water (DissoCubes, SkyePharma) or alternatively in non-aqueous media or water-reduced media (Nanopure, PharmaSol Berlin). A first combinative technology (precipitation followed by high pressure homogenization) is known as NANOEDGETM technology (Baxter). Relatively long milling times, high numbers of homogenization cycles or solvent residues are typical drawbacks of the existing technologies. In order to overcome the limitations of the existing technologies a new combination method was developed for the production of ultra-fine submicron suspensions. The method involves an evaporation step to provide a solvent-free modified starting material followed by high pressure homogenization to produce ultrafine drug nanocrystals. In this study it could be shown that modified hydrocortisone acetate was particularly suitable to be further processed by high pressure homogenization. In comparison to jet-milled hydrocortisone acetate powder the high pressure homogenization of spray-dried hydrocortisone acetate powder resulted in much more homogeneously dispersed nanosuspensions. By using co-processed, spray-dried material (9:1 drug/poloxamer 188 ratio) the required number of homogenization cycles to obtain nanosuspensions was distinctly reduced. In case of the modified material only 1 homogenization cycle at 1500 bar was sufficient to obtain a particle size smaller than that after 20 homogenization cycles using the jet-milled drug powder. The obtained nanosuspensions have shown excellent long-term storage stability.

Anti-Inflammatory Agents↗