Facilitated transdermal delivery of therapeutic peptides and proteins by iontophoretic delivery devices

Chien, Yie W.; Lelawongs, P.; Siddiqui, Ovais; Sun, Yi-Ming; Shi, Weimin

doi:10.1016/0168-3659(90)90017-n

Cited by 59 publications

(24 citation statements)

References 35 publications

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“…Electroosmosis and enhance ment of skin permeability have also to be con sidered [for a review see ref. [1][2][3]. Indeed, pre vious studies have shown that postiontophoretic passive diffusion flux of water or of sev eral drugs was increased as compared to the preiontophoretic transdermal migration by diffusion [3][4][5], Nevertheless, with the excep tion of clinical observations, few instrumental investigations were performed on skin integri ty after iontophoretic treatment [for a review see ref .…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Investigation of Human Skin after in vivo Iontophoresis

Thysman

Neste²,

Préat³

1995

Skin Pharmacol Physiol

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The main objective of our study was to investigate skin function and structure in human volunteers after electrical current application in order to demonstrate the safety of iontophoresis in vivo. The direct current was applied for 30 min at a density of 0.1 and 0.2 mA/cm². Iontophoresis increased cutaneous blood flow as measured by laser Doppler flowmetry (LDF). This increase was reversible within 1 h and was more pronounced at higher current density. Measurements of transepidermal water loss (TEWL) and LDF were the same at the cathode and the anode sites. Except for 5 min at 0.2 mA/cm² density, TEWL values were not enhanced as compared to control values (no iontophoresis). Attenuated total reflectance-Fourier transform infrared spectroscopy of the stratum corneum structure showed a transient increase (30 min) in hydra-tion after electrode application for 30 min. No alteration in lipid structure could be shown. These results augur the safety of drug delivery by iontophoresis.

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Section: Introductionmentioning

confidence: 99%

Noninvasive Investigation of Human Skin after in vivo Iontophoresis

Thysman

Neste²,

Préat³

1995

Skin Pharmacol Physiol

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“…The amount of drug that migrated by iontophoresis was the sum of the amount moved by passive diffusion, current application and electroosmosis. [11][12][13] Furthermore, the amount due to passive diffusion was closely related to the reduction in skin barrier function. 1) Thus, the reduction in barrier function caused by pulsed iontophoresis is important to clarifying the migration of a drug.…”

mentioning

confidence: 99%

Evaluation of Skin Barrier Function Using Direct Current II: Effects of Duty Cycle, Waveform, Frequency and Mode.

Kanebako¹,

Inagi²,

Takayama

2002

Biological & Pharmaceutical Bulletin

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The aim of this study was to evaluate the reduction in skin barrier function caused by pulsed iontophoresis by measuring resistance in the short term. Experiments under direct current (DC) and pulsed direct current (PDC) conditions were carried out using rat abdominal skin in vivo. The resistance was measured every 62.5 m ms and analyzed using a two-compartment model consisting of surface and skin resistance. Moreover, the initial value and the rate constant of surface resistance were calculated with the non-linear approximation program. Using this method, effects of duty cycle, waveform, frequency and mode on the skin barrier function were examined. The barrier function decreased with increasing duty cycle. With regard to waveforms, the influence on the skin barrier function was greatest in the order of sine, rectangular, saw and triangular waveforms. A frequency of less than 100 Hz reduced the barrier function. Considering the reduction in barrier function and skin polarization, the PDC of a rectangular waveform (around 75% as duty cycle and less than 100 Hz as frequency) or sine waveform was most suitable. In addition, the difference in the amount of drug delivered by DC and by PDC was discussed.

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“…1) It is known that the barrier function of skin is disturbed by iontophoresis. [2][3][4] The delivery of drugs by iontophoresis has been evaluated using the Nernst-Planck equation, 5,6) the modified Nernst-Planck equation, [7][8][9] the efficiency of drug delivery calculated from the delivery rate [10][11][12] and the migration in blood circulation based on the pharmacokinetics of drugs. 13) The migration of a drug on the application of a current has been analyzed in detail with these methods.…”

mentioning

confidence: 99%

Transdermal Delivery of Indomethacin by Iontophoresis.

Kanebako¹,

Inagi²,

Takayama

2002

Biological & Pharmaceutical Bulletin

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The objective of this study was to construct a modified equation for the delivery of a drug by iontophoresis. Indomethacin was selected as a model since it has been widely used as a non-steroidal anti-inflammatory drug (NSAID) for external pharmaceutical preparations. The experiments were performed under a constant current in vivo using rat abdominal skin, and the plasma concentration was monitored by HPLC. Pharmacokinetic parameters were obtained from the plasma concentration profiles after intravenous injection. A theoretical value of the transdermal delivery of drug by iontophoresis was calculated from the plasma concentration and pharmacokinetic parameters. The experimental value was evidently higher than the theoretical one, suggesting the enhancement of passive diffusion with an increase of applied current. The modified equation was proposed for the delivery of a drug by iontophoresis incorporating enhanced passive diffusion.

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Facilitated transdermal delivery of therapeutic peptides and proteins by iontophoretic delivery devices

Cited by 59 publications

References 35 publications

Noninvasive Investigation of Human Skin after in vivo Iontophoresis

Noninvasive Investigation of Human Skin after in vivo Iontophoresis

Evaluation of Skin Barrier Function Using Direct Current II: Effects of Duty Cycle, Waveform, Frequency and Mode.

Transdermal Delivery of Indomethacin by Iontophoresis.

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