The efflux transporter P-glycoprotein (P-gp) affects the pharmacokinetics of many drugs. Currently used methods for characterization of P-gp's functional activity in vivo involve the use of radiolabeled substrates, are costly, and are technically demanding. Our objective was to evaluate whether the FDA-approved near-infrared compound indocyanine green (ICG) can be used as a probe substrate of P-gp. We also characterized the interaction of ICG with another efflux transporter, the breast cancer resistance protein (BCRP). We evaluated ICG accumulation and transport in MDCK cells overexpressing P-gp or BCRP (MDCK-MDRI and MDCK-BCRP, respectively) compared to control MDCK cells, in the presence or the absence of transporter inhibitors. In vivo imaging of ICG biodistribution in mice was conducted over 3.5 h using valspodar as the P-gp inhibitor. The EC50 values for ICG accumulation in control MDCK and MDCK-MDR1 cells were 9.0 x 10(-6) +/- 5.7 x 10(-7) M and 1.5 x 10(-5) +/- 1.1 x 10(-6) M, respectively. The efflux ratio for ICG in MDCK-MDR1 cells was 6.8-fold greater than in control cells. P-gp inhibition attenuated ICG efflux from MDR1-MDCK cells, and their effects in those cells were greater than in control MDCK cells. In contrast, BCRP level of expression or pharmacological inhibition did not significantly affect ICG cellular accumulation. In vivo imaging indicated enhanced cerebral ICG distribution with valspodar (brain - foot area under the concentration-time curves of 3.0 x 10(10), 5.6 x 10(10) and 3.7 x 10(19) h.[p/s/sr]/mu W in valspodar-treated mice vs 9.0 x 10(9) and 5.3 x 10(9) h.[p/s/sr]/mu W in controls). The findings from this pilot study suggest that near-infrared imaging using ICG as the probe substrate should be further characterized as a methodology for in vivo evaluation of P-gp activity.

Carbon nanotube (CNTs) inks may provide an effective route for producing flexible electronic devices by digital printing. In this paper we report on the formulation of highly concentrated aqueous CNT inks and demonstrate the fabrication of flexible electroluminescent (EL) devices by inkjet printing combined with wet coating. We also report, for the first time, on the formation of flexible EL devices in which all the electrodes are formed by inkjet printing of low-cost multi-walled carbon nanotubes (MWCNTs). Several flexible EL devices were fabricated by using different materials for the production of back and counter electrodes: ITO/MWCNT and MWCNT/MWCNT. Transparent electrodes were obtained either by coating a thin layer of the CNTs or by inkjet printing a grid which is composed of empty cells surrounded by MWCNTs. It was found that the conductivity and transparency of the electrodes are mainly controlled by the MWCNT film thickness, and that the dominant factor in the luminance intensity is the transparency of the electrode.

This study presents a method for one-step formation of poly(ethylene oxide) nanofibers incorporating, nanoparticles of a poorly water-soluble compound. Using the new method reported here, nanofiber-nanoparticle composites are fabricated in one step by electrospinning of an oil-in-water microemulsion, in which a model material, propylparaben, has been dissolved within the volatile dispersed phase in the presence of a high-molecular-weight polymer. The approach is based on nanoscale confinement to the dispersed phase of an oil-in-water microemulsion with a volatile oil phase, in which the poorly water-soluble materials are dissolved. Thus, when the thermodynamically stable oil-in-water microemulsion is combined with the rapid evaporation of solvent inherent in the electrospinning process, the droplets are converted into organic nanoparticles embedded within a polymeric nanofiber. In addition to possessing process simplicity, this method exhibits a very high percentage of nanopartide loading with desirable active material properties. Specifically, the diameter of the nanofibers is in the range of 60-185 nm, and propylparaben exists within the nanofiber as nanocrystals of 30-120 nm. These dimensions suggest that the nanofiber nanocrystal composites could serve as a delivery system for water-insoluble materials.

Systemic antipsoriatic therapies have potentially life-threatening, long-term side effects. The efficacy of topical drugs is poor, but may be improved by the use of delivery systems based on drug nanoparticles. To produce nanoparticles (NP) composed of cyclosporin A, a classical antipsoriatic drug, and to investigate their penetration and biological effects in human skin affected by psoriatic symptoms, poly-e-caprolactone (PCL) and cyclosporin A (CsA) NP were prepared by the solvent evaporation method. Skin penetration was followed using fluorescently labeled NP in human skin organ cultures (hSOC). Psoriatic symptoms were mimicked in hSOC by the treatment with epidermal growth factor (EGF) and bacterial lipopolysaccharide (LPS). Cell viability in hSOC was evaluated by the resazurin test, and cytokine secretion into the growth medium was measured by immunodetection. We showed that topically applied NP diffused throughout the epidermis within two hours and through the dermis within the following day. They significantly reduced the secretion of inflammatory cytokines IL1 beta, IL6, IL8, IL20 and IL23. At active doses, no cytotoxicity was detected. This type of NP display relevant properties for the use as topical anti-inflammatory agents and may help to resorb psoriatic lesions.