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  • 1
    ISSN: 1573-904X
    Keywords: transdermal drug delivery ; fluorescence measurements ; deconvolution ; flow-through system ; electroporation ; percutaneous transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A fluorescence measurement system and methods of data analysis were developed to measure rapid kinetics of transdermal transport in vitro. Three variations on the technique were demonstrated, where the receptor compartment concentration was determined by: 1) fluorescence measurements of aliquots removed at discrete time points, 2) continuous fluorescence measurements made directly in the receptor compartment using a custom-made fluorimeter cuvette as a permeation chamber, and 3) continuous fluorescence measurements made in a flow-through cuvette containing receptor solution continuously pumped from a flow-through permeation chamber. In each case, the measured signal was a convolution of the time-dependent molecular flux (the desired information) and the characteristic response of the measurement system. Algorithms for deconvolution of the signal were derived theoretically. For the most complicated case, (3), the experimental confirmation is shown here, proving a time resolution on the order of half a minute.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: cavitation ; drug delivery ; sonoporation ; bovine erythrocyte ; hemolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Ultrasound has been shown to transiently permeabilize biological membranes, thereby facilitating delivery of large compounds such as proteins and DNA into cells and across tissues such as skin. In this study, we sought to quantitatively determine the dependence of cell membrane permeabilization on ultrasound parameters and to identify acoustic signals which correlate with observed membrane permeabilization. Methods. Bovine red blood cells were exposed to ultrasound at 24 kHz over a range of controlled conditions. The degree of membrane permeabilization was measured by release of hemoglobin and was determined as a function of ultrasound parameters and measured acoustic signals. Results. These studies showed that permeabilization increased with incident ultrasound pressure, increased with total exposure time above a threshold of approximately 100 msec, showed a weak dependence on pulse length with a small maximum at 3 msec, and did not depend on duty cycle under the conditions examined. Using measured acoustic spectra we found that red blood cell membrane permeabilization correlated best with the pressure measured at half the driving frequency (f/ 2=12 kHz) and its ultraharmonics, less strongly with the broadband noise pressure measured between peaks, and least strongly with pressure measured at the driving frequency and its higher harmonics. Permeabilization caused by ultrasound applied at any set of conditions tested in this study could be well predicted by the parameter τ⋅Pf /2, which characterizes the total cavitational exposure. Conclusions. This study provides a quantitative guide to designing ultrasound protocols useful for drug delivery. The acoustic measurements support the hypothesis that ultrasonic cavitation is the mechanism by which membranes are permeabilized. They also suggest that measurable acoustic signals can provide noninvasive, real-time feedback about membrane permeabilization and drug delivery.
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  • 3
    ISSN: 1573-904X
    Keywords: macromolecule ; electroporation ; iontophoresis ; skin ; permeation enhancer ; transdermal transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract 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 trandermal transport enhancers uniquely suited to skin electroporation.
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature biotechnology 24 (2006), S. 416-417 
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] Despite the increasing importance of protein therapeutics and vaccines, the need to deliver them by hypodermic injection remains a major limitation. Delivery of protein drugs through the skin is an attractive alternative to needles, but has proved elusive thus far. Findings reported by Chen et al. ...
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  • 5
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] Therapeutic uses of compounds produced by biotechnology are presently limited by the lack of non-invasive methods for continuous administration of biologically-active macromolecules. Transdermal delivery would be an attractive solution, except macromolecules have not previously been delivered ...
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  • 6
    ISSN: 1573-904X
    Keywords: transdermal drug delivery ; electroporation ; iontophoresis ; human skin ; percutaneous transport ; flow-through system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract By incorporating techniques adapted from the microelectronics industry, the field of microfabrication has allowed the creation of microneedles, which have the potential to improve existing biological-laboratory and medical devices and to enable novel devices for gene and drug delivery. Dense arrays of microneedles have been used to deliver DNA into cells. Many cells are treated at once, which is much more efficient than current microinjection techniques. Microneedles have also been used to deliver drugs into local regions of tissue. Microfabricated neural probes have delivered drugs into neural tissue while simultaneously stimulating and recording neuronal activity, and microneedles have been inserted into arterial vessel walls to deliver antirestenosis drugs. Finally, microhypodermic needles and microneedles for transdermal drug delivery have been developed to reduce needle insertion pain and tissue trauma and to provide controlled delivery across the skin. These needles have been shown to be robust enough to penetrate skin and dramatically increase skin permeability to macromolecules.
    Type of Medium: Electronic Resource
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