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    ABSTRACT: To target adenoviral vectors to cells of the vasculature and shielding vectors from inactivation by the immune system. Complexes of reporter gene expressing adenoviral vectors with positively charged magnetic nanoparticles were formed by electrostatic interaction in presence or absence of additional negatively charged poly(ethylene glycol)-based polymer. Transduction of HUVEC was analyzed in vitro under flow. Protection from inactivation by the immune system was analyzed by pre-incubation of AdV and complexes with neutralizing antibodies and subsequent reporter protein analysis of infected cells. Physical association of AdV with MNP and polymers was demonstrated by radioactive labelling of components and co-sedimentation in a magnetic field. Ad-MNP+/-polymer resulted in efficient transduction of HUVEC, depending on MOI and flow rate in presence of magnetic field, whereas no transduction was observed without complex formation with MNP or in absence of magnetic field. Association with MNP did result in protection from neutralizing antibodies, with slightly increased protection provided by the polymer. Complex formation of AdV with MNP is a viable means for targeting of vectors to areas of magnetic field gradient. Additional coating with polymer might proof useful in protection from inactivation by the immune system.
    Pharmaceutical Research 12/2011; 29(5):1219-31. · 4.74 Impact Factor
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    ABSTRACT: Dispersion based products have applications in every area of life. During formulation of new products the dispersion properties have to be adjusted to obtain the desired stability, textural and rheological properties. Most often stable colloidal dispersions are required, sometime however, weak flocculation is purposely induced to adjust structural properties. In other cases strong flocculation is helpful for dispersion separation. From this it is evident that classification of the state of a dispersion regarding flocculation (net attractive particle interaction) and quantification of its degree are necessary and routine tasks in every day formulation and optimization work. Zeta potential is commonly used to predict the stability of virtually all colloidal dispersions. This neglects that the Zeta potential concept is limited to classical electrostatically stabilized dispersions. It has to be emphasized, however, that nowadays new dispersion products are stabilized by different approaches (e.g. by steric or rheological stabilization). Sedimentation analysis by multisample analytical centrifugation with photometric detection is a rather simple but powerful and high throughput method to characterize the dispersed state/degree of particle interaction. Visualization of in situ separation behaviour allows for the classification and differentiation between the various instability phenomena such as swarm sedimentation (stable dispersion) and zone sedimentation (flocculation, agglomeration). Even more, complex systems with subfractions of particles exhibiting a different behaviour can also be analyzed. Sedimentation behaviour of different dispersions made from plain or decorated nanoparticles as a function of pH of the continuous phase is presented and analyzed in terms of the degree and type of flocculation and compared with predictions based on Zeta potential data. Results demonstrate that contrary to measured Zeta potential the colloidal stability of the dispersed particles and the degree of particle flocculation/agglomeration were always well predicted by the sedimentation behaviour.
    Colloids and Surfaces A Physicochemical and Engineering Aspects 01/2013; · 2.11 Impact Factor
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    ABSTRACT: Magnetic nanoparticles (MNPs) and magnets can be used to enhance gene transfer or cell attachment but gene or cell delivery to confined areas has not been addressed. We therefore searched for an optimal method to simulate and perform local gene targeting and cell delivery in vitro. Localized gene transfer or cell positioning was achieved using permanent magnets with newly designed soft iron tips and MNP/lentivirus complexes or MNP-loaded cells, respectively. Their distribution was simulated with a mathematical model calculating magnetic flux density gradients and particle trajectories. Soft iron tips generated strong confined magnetic fields and could be reliably used for local (~500 μm diameter) gene targeting and positioning of bone marrow cells or cardiomyocytes. The calculated distribution of MNP/lentivirus complexes and MNP-loaded cells concurred very well with the experimental results of local gene expression and cell attachment, respectively. MNP-based gene targeting and cell positioning can be reliably performed in vitro using magnetic soft iron tips, and computer simulations are effective methods to predict and optimize experimental results.
    Pharmaceutical Research 12/2011; 29(5):1380-91. · 4.74 Impact Factor


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Jun 3, 2014