A novel concept was developed here for the continuous, contact- and contamination-free treatment of fluid mixtures with ultrasound. It is based on exciting a steel jacket with an ultrasonic transducer, which transmitted the sound waves via pressurised water to a glass tube installed inside the jacket. Thus, no metallic particles can be emitted into the sonicated fluid, which is a common problem when a sonotrode and a fluid are in direct contact. Moreover, contamination of the fluid from the environment can be avoided, making the novel ultrasonic flow-through cell highly suitable for aseptic production of pharmaceutical preparations. As a model system, vegetable oil-in-water emulsions, fed into the cell as coarse pre-emulsions, were studied. The mean droplet diameter was decreased by two orders of magnitude yielding Sauter diameters of 0.5 microm and below with good repeatability. Increasing the residence time in the ultrasonic field and the sonication power both decreased the emulsion mean diameter. Furthermore, the ultrasonic flow-through cell was found to be well suited for the production of nanoparticles of biodegradable polymers by the emulsion-solvent extraction/ evaporation method. Here, perfectly spherical particles of a volume mean diameter of less than 0.5 microm could be prepared. In conclusion, this novel technology offers a pharmaceutically interesting platform for nanodroplet and nanoparticle production and is well suited for aseptic continuous processing.

Recognition of antigens by immunocompetent cells involves interactions that are specific to the chemical sequence and conformation of the epitope (antigenic determinant). Adjuvants that are currently used to enhance immunity to antigens tend to either alter the antigen conformation through surface adsorption or shield potentially critical determinants, e.g., functional groups. It is demonstrated here that surface-modified diamond nanoparticles (5-300 nm) provide conformational stabilization, as well as a high degree of surface exposure to protein antigens. By enhancing the availability and activity of the antigen in vivo, a strong, specific immune response can be elicited. Results are demonstrated for mussel adhesive protein (MAP), a substance for which conventional adjuvants have proven only marginally successful in evoking an immune response. Surface-modified diamond nanoparticles as antigen delivery vehicles are a novel example of the exciting marriage of materials science, chemistry, and biology.

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Sulfonic poly(styrene-co-divinylbenzene) ion-exchange resins are commonly employed as supported acid catalysts or as selective sorbents in a number of different applications. Using the reaction of acetic acid and methanol to form methyl acetate and water as a model system, the competitive sorption behavior of the corresponding nonreactive binary pairs was studied for macroporous, highly cross-linked resins of different acid loading. It was found that a reduction of the acid loading decreases the resins' selectivity toward the sorption of water and increases its affinity toward less polar species, e.g., methyl acetate. To describe the sorption behavior a phase equilibrium model based on the Flory-Huggins theory of polymer swelling was developed, taking into account the hydration of the acid sites upon the sorption of water. The ability of the model to represent the competitive sorption behavior as a function of the resin's acid loading has been demonstrated by comparison with various sets of experimental equilibrium data. Finally, initial work to characterize the catalytic performance for different degrees of sulfonation is presented, and conclusions toward the application of these resins as stationary phases for reactive chromatography are drawn.

The potential of a static micromixer for the production of protein-loaded biodegradable polymeric microspheres by a modified solvent extraction process was examined. The mixer consists of an array of microchannels and features a simple set-up, consumes only very small space, lacks moving parts and offers simple control of the microsphere size. Scale-up from lab bench to industrial production is easily feasible through parallel installation of a sufficient number of micromixers ('number-up'). Poly(lactic-co-glycolic acid) microspheres loaded with a model protein, bovine serum albumin (BSA), were prepared. The influence of various process and formulation parameters on the characteristics of the microspheres was examined with special focus on particle size distribution. Microspheres with monomodal size distributions having mean diameters of 5-30 micro m were produced with excellent reproducibility. Particle size distributions were largely unaffected by polymer solution concentration, polymer type and nominal BSA load, but depended on the polymer solvent. Moreover, particle mean diameters could be varied in a considerable range by modulating the flow rates of the mixed fluids. BSA encapsulation efficiencies were mostly in the region of 75-85% and product yields ranged from 90-100%. Because of its simple set-up and its suitability for continuous production, static micromixing is suggested for the automated and aseptic production of protein-loaded microspheres.