Searching for the new normal: the rebuilding process for risk management - a conference summary

The Chicago Fed’s Supervision and Regulation Department, in conjunction with DePaul University’s Center for Financial Services, sponsored its third annual Financial Institution Risk Management Conference on April 6–7, 2010. The conference concentrated on comprehensive risk management, lessons learned, and headline issues.Risk ; Risk management

Risks and resolutions: the ‘day after’ for financial institutions - a conference summary

The Chicago Fed’s Supervision and Regulation Department, in conjunction with DePaul University’s Center for Financial Services, sponsored its second annual Financial Institutions Risk Management Conference on April 14–15, 2009. The conference focused on risk management, headline issues, and recent financial innovations.Financial institutions ; Risk

A Hydrogel/Carbon-Nanotube Needle-Free Device for Electrostimulated Skin Drug Delivery

The permeability of skin allows passive diffusion across the epidermis to reach blood vessels but this is possible only for small molecules such as nicotine. In order to achieve transdermal delivery of large molecules such as insulin or plasmid DNA, permeability of the skin and mainly the permeability of stratum corneum has to be increased. Moreover, alternative routes that avoid the use of needles will improve the quality of life of patients. A method named “electropermeabilization” has been shown to increase skin permeability. Here, we report the fabrication of an innovative hydrogel, made of nanocomposite material. This nanocomposite device aims at permeabilizing the skin and delivering drug molecules at the same time. It includes a biocompatible polymer matrix (hydrogel) and double walled-carbon-nanotubes (DWCNTs) in order to bring electrical conductivity and improve mechanical properties. Carbon nanotubes and especially DWCNTs are ideal candidates, combining high electrical conductivity with a very high specific surface area together with a good biocompatibility when included into a material. The preparation and characterization of the nanocomposite hydrogel as well as first results of electro stimulated transdermal delivery using an ex vivo mouse skin model are presented

Transdermal Drug Delivery Aided by an Ultrasound Contrast Agent: An In Vitro Experimental Study

Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity® in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD)

Mechanistic studies of skin electroporation using biophysical methods

The mechanism by which high-voltage pulses transiently disrupt lipid bilayers in cell membranes has been the subject of controversy since electroporation was first observed almost three decades ago. Determining the mechanism by which such pulses permeabilize the complex, multilamellar bilayer structures in skin poses an even greater challenge. To address this issue, a range of methods have been employed to perform biophysical characterization for skin electroporation studies. In this chapter, we provide an overview of these methods and highlight representative findings which biophysical characterization has yielded

Macromolecules as novel transdermal transport enhancers for skin electroporation

PURPOSE: Macromolecules were investigated as chemical enhancers of transdermal transport by skin electroporation. Although unable to enhance passive or iontophoretic transport, macromolecules are proposed to enhance electroporation-assisted delivery by stabilizing the increased permeability caused by high-voltage pulses. METHODS: To test this hypothesis, we examined the timescale of transport, the influence of electrical protocol and the influence of macromolecule size, structure, and charge on enhancement of transdermal mannitol transport in vitro by heparin, dextran-sulfate, neutral dextran, and poly-lysine. RESULTS: Skin electroporation increased transdermal mannitol delivery by approximately two orders of magnitude. The addition of macromolecules further increased transport up to five-fold, in support of the proposed hypothesis. Macromolecules present during pulsing enhanced mannitol transport after pulsing for hours, apparently by a macromolecule-skin interaction. No enhancement was observed during passive diffusion or low-voltage iontophoresis, suggesting that macromolecules interact specifically with transport pathways created at high voltage. Although all macromolecules studied enhanced transport, those with greater charge and size were more effective. CONCLUSIONS: This study demonstrates that macromolecules can be used as transdermal transport enhancers uniquely suited to skin electroporation

Analysis of sialoadhesin expression on mouse alveolar macrophages

Sialoadhesin (Sn) is a macrophage-restricted receptor that was first characterised on mouse resident bone marrow macrophages as a receptor that mediates the binding, without ingestion, of sheep erythrocytes. Sn is highly conserved in mammals but its expression on tissue macrophages is heterogeneous. In the mouse, high levels of erythrocytes binding are shown on macrophages from lymphoid tissues but a low erythrocytes binding activity is detectable on macrophages isolated from the broncho-alveolar space. Yet, Sn expression has been demonstrated on human, rat and pig alveolar macrophages (AM) using methods of molecular biology. Therefore, the present study aimed to investigate the expression of Sn on mouse AM in order to confirm the presence of the protein on this population of murine macrophages. Using cytometrical analyses, we showed that Sn was expressed on mouse AM surface. Following desialylation, AM largely bound erythrocytes and this binding was inhibited by 3D6, an anti-mouse Sn monoclonal antibody, in a dose-dependent manner. This indicates that Sn is expressed on mouse AM but that the sialic acid binding activity mediated by this molecule is naturally masked by endogenous sialic acid within the glycocalyx on the cell surface