Biomedical subjects

Heinrich Hofmann

Publications and source records attributed to Heinrich Hofmann.

7 recordsLinked to original sources

PubMed2006

Precipitation of nanostructured copper oxalate: substructure and growth mechanism.

The possibility of controlling materials properties by tailoring their substructure at the nanometer scale is a current topic of great interest. To do so, a fundamental understanding of the growth mechanism is of key importance and an analytical challenge as nanostructured materials are often produced by precipitation methods at high supersaturations where formation kinetics are fast. The current study focuses on the precipitation of copper oxalate, which has been previously shown to produce self-assembled ordered nanostructured particles with the promise of being able to tailor this nanometer substructure. In the current study we investigate in detail the growth mechanism and kinetics of precipitation by using in-situ particle size measurement or by stopping the reaction at various stages and using ex-situ methods. Combining the ex-situ methods of high-resolution scanning electron microscopy, transmission electron microscopy, and X-ray powder diffraction along with the in-situ methods, we were able to follow the growth process from 2 min to 2 weeks. The results in the 2-30 min period lead to the proposal of a core-shell growth model with a poorly ordered core and a well-structured shell of nanosized crystallites (50-70 nm), adding support to the brick-by-brick model previously proposed for this phase of particle growth. Particle evolution over long periods up to 2 weeks show a ripening which produces lens-shaped particles that eliminate the "high" surface energy faces observed in the earlier stages of growth. A more complete growth mechanism for copper oxalate precipitation at moderate supersaturations is proposed similar to recent findings for other self-assembled nanostructured particles.

Chemical Precipitation↗

PubMed2006

Interaction of functionalized superparamagnetic iron oxide nanoparticles with brain structures.

Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) combined with magnetic resonance imaging (MRI) are under clinical evaluation to enhance detection of neurodegenerative diseases. A major improvement would be to link therapeutic drugs to the SPIONs to achieve targeted drug delivery, either at the cell surface or intracellularly, together with active disease detection, without inducing cell reaction. Our objectives were to define the characteristics of SPIONS able to achieve cell-specific interaction with brain-derived structures. Our system consisted in an iron oxide core (9-10 nm diameter) coated either with dextran (Sinerem and Endorem) or various functionalized polyvinyl alcohols (PVAs) (PVA-SPIONs). We investigated the cellular uptake, cytotoxicity, and interaction of these various nanoparticles with brain-derived endothelial cells, microglial cells, and differentiating three-dimensional aggregates. None of the nanoparticles coated with dextran or the various PVAs was cytotoxic or induced the production of the inflammatory mediator NO used as a reporter for cell activation. AminoPVA-SPIONs were taken up by isolated brain-derived endothelial and microglial cells at a much higher level than the other SPIONs, and no inflammatory activation of these cells was observed. AminoPVA-SPIONs did not invade brain cells aggregates lower than the first cell layer and did not induce inflammatory reaction in the aggregates. Fluorescent aminoPVA-SPIONs derivatized with a fluorescent reporter molecule and confocal microscopy demonstrated intracellular uptake by microglial cells. Fluorescent aminoPVA-SPIONs were well tolerated by mice. Therefore, functionalized aminoPVA-SPIONs represent biocompatible potential vector systems for drug delivery to the brain that may be combined with MRI detection of active lesions in neurodegenerative diseases.

Animals↗

PubMed2006

Enhancement of the efficiency of non-viral gene delivery by application of pulsed magnetic field.

New approaches to increase the efficiency of non-viral gene delivery are still required. Here we report a simple approach that enhances gene delivery using permanent and pulsating magnetic fields. DNA plasmids and novel DNA fragments (PCR products) containing sequence encoding for green fluorescent protein were coupled to polyethylenimine coated superparamagnetic nanoparticles (SPIONs). The complexes were added to cells that were subsequently exposed to permanent and pulsating magnetic fields. Presence of these magnetic fields significantly increased the transfection efficiency 40 times more than in cells not exposed to the magnetic field. The transfection efficiency was highest when the nanoparticles were sedimented on the permanent magnet before the application of the pulsating field, both for small (50 nm) and large (200-250 nm) nanoparticles. The highly efficient gene transfer already within 5 min shows that this technique is a powerful tool for future in vivo studies, where rapid gene delivery is required before systemic clearance or filtration of the gene vectors occurs.

Animals↗

PubMed2006

Formation and drying of colloidal crystals using nanosized silica particles.

Much interest has been generated in the fabrication of colloidal crystals from suspensions because of the promise of photonic band gap applications. However, since the case of small, nonsedimenting colloidal particles indeed remains rather rarely treated, spherical silica particles with diameters varying from 75 down to 20 nm have been used in the present work to fabricate colloidal crystals by drying the suspending liquid. Typical events that take place during the drying process of a particulate film, such as cracking, compaction and penetration of air into a porous network, have been evaluated using existing theories, and the maximum stress in the drying film could be approximated. Investigation on the dry film structure by scanning electron microscopy showed the arrangement of particles in a close-packed system. To interpret the formation of such crystals, the amplitudes of the interparticle and capillary forces have been estimated from existing models. The repulsive interparticle forces allow the particles to remain stable and thus rearrange up to fairly high particle concentration. These modeling results showed the dominance of the capillary contribution at the end of the drying process. Nitrogen adsorption/desorption measurements gave very coherent results regarding both pore volume and pore size of the dry particulate films when compared to the expected ordered packing arrangements.

Journal Article↗

PubMed2005

Use of seeds to control precipitation of calcium carbonate and determination of seed nature.

Understanding and controlling precipitation reactions is a major challenge for industrial crystallization. Calcium carbonate is a widely studied system: more than 3000 papers have been devoted to the subject over the past 10 years. The first step of the precipitation of calcium carbonate, from relatively concentrated solutions (0.01 mol/L), involves the formation of an initial gel phase which later transforms into calcite, vaterite, or a mixture of both phases. Our work aimed at controlling this first step. Nanosized seeds (8 nm), formed in situ, were used in order to control the often chaotic nucleation step which normally leads to poor phase selection and broad particle size distributions. Seeding has often been used to avoid spontaneous nucleation in metastable solutions for growth mechanism investigations of single-crystal calcium carbonate. Here the ability of a seeding method to control the precipitation reaction evolution even in the case of high supersaturation is demonstrated. The seeds and the presence of a polymeric additive (poly(acrylic acid)) allow the control of the precipitated polymorph and the specific surface area, while maintaining a narrow particle size distribution in the submicron range. Direct characterization methods did not succeed in identifying these nanoseeds; indirect methods using solubility calculations are used to demonstrate their existence and quantify size and number density of the nanosized seeds.

Calcium Carbonate↗

PubMedDate not supplied

Systemic distribution and elimination of plain and with Cy3.5 functionalized poly(vinyl alcohol) coated superparamagnetic maghemite nanoparticles after intraarticular injection in sheep in vivo.

PVA coated and fluorescent dye (Cy3.5) functionalized vinyl alcohol/vinyl amine copolymer coated superparamagnetic iron oxide nanoparticles (SPION) were evaluated for systemic distribution and elimination after intraarticular injection in sheep. Observation was done at 3, 24, 72, and 120 hours after injection using light microscopy, fluorescent microscopy, and confocal microscopy. No pathologic influence of SPION on the tissue harvested could be seen. A significantly increased iron content could be identified in the kidneys, lymph nodes, and spleen after injection of SPION. No particles were detected in the liver, the urinary, and the gall bladder. No positive fluorescent signal could be attributed to SPION throughout the organs. Our results indicated that the iron component of the SPION is possible to be incorporated into the physiologic iron metabolism after reabsorption in the proximal tubule system of the kidney and that concentration levels of Cy3.5 are too low to be detected throughout the body.

Animals↗

PubMedDate not supplied

Uptake and biocompatibility of functionalized poly(vinylalcohol) coated superparamagnetic maghemite nanoparticles by synoviocytes in vitro.

Superparamagnetic iron oxide nanoparticles (SPION) were coated with either Polyvinyl alcohol (PVA) or Vinyl alcohol/vinyl amine copolymer and further functionalized with the fluorochromes Cy3.5 or Texas Red. A colloidally stable suspension of nanoparticles was incubated on sheep synovial cells in vitro for 3, 24, 72, and 120 hours. Nanoparticle internalization into synoviocytes as well as biocompatibility was visualized using light, fluorescence and confocal microscopy and fluorochrome labeled cells were quantified by flow cytometry. Data were analyzed by ANOVA factorial tests. Amino-PVA-SPION alone was detectable in cytoplasmic endosome-like structures after 3 hours of incubation but resulted in early cell death after 24 hours. Although amino-PVA-Cy3.5-SPION and PVA-TexasRed-SPION were taken up more slowly and less intensely, both labeled more than 80% of the cells in culture, but did not significantly change cell morphology or vitality at any time of evaluation in comparison to control cells. Results indicate that functionalized amino PVA-coated SPION are biocompatible, were successfully internalized by synoviocytes and hold promise for future biomedical applications utilizing magnetic drug targeting in joint disease.

Animals↗