Andreas K. Schaper

Nanostructured Fibers via Electrospinning

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Polymer, Metal, and Hybrid Nano‐ and Mesotubes by Coating Degradable Polymer Template Fibers (TUFT Process)

). Selective reaction with the silver atoms at the interface of the particles occurred and the coated particles were then extracted from reverse micelles. The powder of coated nanocrystals thus obtained was then dispersed in hexane, giving an optically clear solution. The size distribution was still rather large (30 %), and to reduce it a size-selected precipitation process [20] was used. In this process two solvents, such as hexane and pyridine, are mixed. The first is a good solvent and the second a poor solvent for the alkyl chains. With this solvent mixture, the larger coated particles flocculated whereas the smaller ones remain in the solution, thus providing size selection. By repeating this process several times, a homogenous clear colloidal solution of dispersed 4.3 nm nanocrystals is obtained. The concentration of nanocrystals with final size distribution around 13 % was controlled.

Poly-L-lactide nanofibers by electrospinning – Influence of solution viscosity and electrical conductivity on fiber diameter and fiber morphology

Abstract Poly-L-lactide (PLA) fibers were obtained by electrospinning of PLA / dichloromethane solutions. Formation of beaded fibers combined with decreased fiber diameters were observed for low PLA concentrations in solution. Increase of the electrical conductivity by addition of pyridinium formiate (PF) caused a significant reduction of bead formation. The electrospinning of dilute PLA / PF / dichloromethane solutions resulted in PLA nanofibers. Systematic variations clearly identified the solution viscosity and the electrical conductivity at otherwise fixed parameters (surface tension, molecular weight, electrode geometry, electrical field, etc.) as crucial parameters for the formation of beads upon electrospinning of PLA / dichloromethane solutions.

Targeting the Blind Spot of Polycationic Nanocarrier-Based siRNA Delivery

Polycationic nanocarriers attract increasing attention to the field of siRNA delivery. We investigated the self-assembly of siRNA vs pDNA with polycations, which are broadly used for nonviral gene and siRNA delivery. Although polyethyleneimine (PEI) was routinely adopted as siRNA carrier based on its efficacy in delivering pDNA, it has not been investigated yet why PEI efficiently delivers pDNA to cells but is controversially discussed in terms of efficacy for siRNA delivery. We are the first to investigate the self-assembly of PEI/siRNA vs PEI/pDNA and the steps of complexation and aggregation through different levels of hierarchy on the atomic and molecular scale with the novel synergistic use of molecular modeling, molecular dynamics simulation, isothermal titration calorimetry, and other characterization techniques. We are also the fist to elucidate atomic interactions, size, shape, stoichiometry, and association dynamics for polyplexes containing siRNA vs pDNA. Our investigation highlights differences in the hierarchical mechanism of formation of related polycation-siRNA and polycation-pDNA complexes. The results of fluorescence quenching assays indicated a biphasic behavior of siRNA binding with polycations where molecular reorganization of the siRNA within the polycations occurred at lower N/P ratios (nitrogen/phosphorus). Our results, for the first time, emphasize a biphasic behavior in siRNA complexation and the importance of low N/P ratios, which allow for excellent siRNA delivery efficiency. Our investigation highlights the formulation of siRNA complexes from a thermodynamic point of view and opens new perspectives to advance the rational design of new siRNA delivery systems.

Multi-wall carbon nanotubes with uniform chirality: evidence for scroll structures

Multi-wall carbon nanotubes (MWCNT) obtained by catalytic decomposition of iron phthalocyanine are investigated by high resolution electron microscopy and electron diffraction (ED). The evaluation of the ED patterns shows that all MWCNTs studied have a uniform chirality, i.e. all tubes of a given MWCNT show the same chiral angle. The conditions for the formation of nested tubes are discussed. A comparison of the values of the chiral angles with those of the corresponding interwall spacings, both obtained from the ED patterns, leads to the conclusion that these MWCNTs have a scroll structure, very probably consisting of one single rolled-up graphene sheet.

Design of Amine-Modified Graft Polyesters for Effective Gene Delivery Using DNA-Loaded Nanoparticles

AbstractPurpose. The purpose of this study was the design of a polymeric platform for effective gene delivery using DNA-loaded nanoparticles. Methods. The polymers were synthesized by carbonyldiimidazole (CDI)-mediated coupling of diamines diethylaminopropylamine (DEAPA), dimethlyaminopropylamine (DMAPA) or diethylaminoethylamine (DEAEA) to poly(vinyl alcohol) (PVA) with subsequent grafting of d,l-lactide and glycolide (1:1) in the stoichiometric ratios of 1:10 and 1:20 (free hydroxyl groups/monomer units). The polymers were characterized by 1H-NMR, gel permeation chromatography-multiple-angle laser-light-scattering, and differential scanning calorimetry. DNA-loaded nanoparticles prepared by a modified solvent displacement method were characterized with regard to their zeta (ζ)-potential and size. The transfection efficiency was assessed with the plasmid DNA pCMV-luc in L929 mouse fibroblasts. Results. The polymers were composed of highly branched, biodegradable cationic polyesters exhibiting amphiphilic properties. The amine modification enhanced the rapid polymer degradation and resulted in the interaction with DNA during particle preparation. The nanoparticles exhibited positive ζ-potentials up to +42 mV and high transfection efficiencies, comparable to polyethlyenimine (PEI) 25kDa/DNA complexes at a nitrogen to phosphate ratio of 5. Conclusions. The polymers combined amine-functions and short poly(D,L-lactic-co-glycolic acid) (PLGA) chains resulting in water-insoluble polymers capable of forming biodegradable DNA nanoparticles through coulombic interactions and polyester precipitation in aqueous medium. The high transfection efficiency was based on fast polymer degradation and the conservation of DNA bioactivity.

Deposition of nanoparticles in the arterial vessel by porous balloon catheters: Localization by confocal laser scanning microscopy and transmission electron microscopy

Restenosis remains the major limitation of percutaneous transluminal angloplasty (PTA) and stenting in the treatment of patients with atherosclerotic disease. Catheter-based local delivery of pharmacologic agents offers a potential therapeutic approach to reducing restenosis and minimizing undesirable systemic side effects. However, the intramural retention of liquid agents is low. Therefore, to achieve a sustained and regional release of the therapeutic agent it must be encapsulated in nanoparticle carrier systems. The purpose of this study was to investigate the size dependence of the penetration of nanoparticles after local delivery into the vessel wall of the aorta abdominalis of New Zealand white rabbits. Two milliliters of a 0.025% fluorescence-labeled polystyrene nanoparticle suspension with diameters ranging from 110 to 514 nm were infused at 2 atm and at constant PTA pressure of 8 atm into the aorta abdominalis. After the infused segments were removed, the location of nanoparticles was visualized using confocal laser scanning microscopy and transmission electron microscopy. The study demonstrates a size-dependent nanoparticle penetration into the intact vessel wall. While nanoparticles of about 100 and 200 nm were deposited in the inner regions of the vessel wall, 514-nm nanoparticles accumulated primarily at the luminal surgace of the aorta. The observations confirm that size plays a critical role in the distribution of particles in the arterial vessel wall. It is additionally influenced by the formation of pressure-induced infusion channels, as well as by the existence of anatomic barriers, such as plaques, at the luminal surface of the aorta or the connective elastic tissue.

Storage stability of optimal liposome–polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery

The delivery of nucleic acids such as DNA or siRNA still represents a major hurdle, especially with regard to possible therapeutic applications in vivo. Much attention has been focused on the development of non-viral gene delivery vectors, including liposomes or cationic polymers. Among them, polyethylenimines (PEIs) have been widely explored for the delivery of nucleic acids and show promising results. The combination of cationic polymers and liposomes (lipopolyplexes) for gene delivery may further improve their efficacy and biocompatibility, by combining the favourable properties of lipid systems (high stability, efficient cellular uptake, low cytotoxicity) and PEIs (nucleic acid condensation, facilitated endosomal release). In this study, we systematically analyse various conditions for the preparation of liposome-polyethylenimine-based lipopolyplexes with regard to biological activity (DNA transfection efficacy, siRNA knockdown efficacy) and physicochemical properties (size, zeta potential, stability). This includes the exploration of lipopolyplex compositions containing different liposomes and different relevant branched or linear low-molecular-weight PEIs. We establish optimal parameters for lipopolyplex generation, based on various PEIs, N/P ratios, lipids, lipid/PEI ratios and preparation conditions. Importantly, we also demonstrate that certain lipopolyplexes retain their biological activity and physicochemical integrity upon prolonged storage, even at 37°C and/or in the presence of serum, thus providing formulations with considerably higher stability as compared to polyplexes. In conclusion, we establish optimal liposome-polyethylenimine lipopolyplexes that allow storage under ambient conditions. This is the basis and an essential prerequisite for novel, promising and easy-to-handle formulations for possible therapeutic applications.

Comparative studies on the electrical and mechanical behavior of catalytically grown multiwalled carbon nanotubes and scrolled graphene

The electrical and mechanical properties of multiwalled carbon nanotubes and of scrolled graphene structures, synthesized from iron-phthalocyanine in a catalytic chemical vapor deposition process, were investigated in situ in a transmission electron microscope. These experiments enabled us to get a more detailed quantitative picture of the peculiarities of the two different types of carbon nanostructures. The nanoscrolls showed superior conductance >10G(o), against ≤1G(o) of the nested tubes, and a much enhanced electric sustainability (∼10(8) A/cm(2)). While the pronounced nonlinear increase in current in the nested tube structure with increasing applied voltage is directly related to an increasing number of tubes involved, the electric breakdown has correspondingly been characterized by fractional ablation of the successive layers. Scrolls, on the contrary, do not show any fractional electric response. Mechanical bending has been found easier with scrolled graphenes than with nested tubes. This observation confirms the prediction of higher flexibility of the scroll structure in interesting phenomena like intercalation and electroactuation.

Influence of morphology and drug distribution on the release process of FITC-dextran-loaded microspheres prepared with different types of PLGA

The aim of the present work was to understand the collaborative roles and the comprehensive effects of polymer nature, morphology, drug distribution and release behaviour for PLGA microspheres prepared by the double emulsion method. The morphology and drug distribution of the FITC-dextran-loaded microspheres were investigated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), respectively. The results show that the morphology and release profiles depend on the polymer nature. For the capped PLGA RG502, the porosity, pore size and drug distribution had no pronounced influence on the release profile beyond the initial release. No significant changes in size and morphology were found and there was negligible water uptake during the release process. PEG addition as a pore maker indicated a possible way to modify the release rate at the second release stage. However, in the case of the uncapped PLGA RG503H, release profiles were dependent upon changes in porosity, pore size and drug loading. Increases in porosity, internal pore size and loading resulted in a continuous release profile. Previous studies have shown the importance of different process parameters on morphology and drug release, but in this work it is clear that polymer nature is a determining factor.