Quantitative Description of the Effect of Molecular Size upon Electroosmotic Flux Enhancement during Iontophoresis for a Synthetic Membrane and Human Epidermal Membrane

Peck, Kendall D.; Srinivasan, V.; Li, S. Kevin; Higuchi, William I.; Ghanem, Abdel‐Halim

doi:10.1021/js950044j

Cited by 42 publications

(52 citation statements)

References 25 publications

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“…an increase in electroosmotic flux enhancement). Peck et al [42] studied the electroosmotic transport behavior across a synthetic membrane and skin and showed that flux enhancement due to electroosmosis was related to the molecular size of a permeant, which is consistent with the predictions from equation 9.…”

Section: Iontophoretic Transport Across the Polar Pathwaymentioning

confidence: 55%

“…Thus, the extent of electroosmosis is related to the thickness of the double layer and the ionic strength of the solution in the pores of the skin. Through these relationships, skin electroosmosis has been used to characterize the skin polar pathway [41,42,43]. …”

Section: Iontophoretic Transport Across the Polar Pathwaymentioning

confidence: 99%

“…The dashed and dashed-dotted lines represent the extrapolations of the Peclet numbers from the positive potential (anodal iontophoresis) to negative potential (cathodal iontophoresis) for mannitol and urea, respectively, assuming a single-pore charge membrane model. Data from Li et al [49] and Peck et al [42]. Cathodal iontophoresis data of sucrose are not available. …”

Section: Iontophoretic Transport Across the Polar Pathwaymentioning

confidence: 99%

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Passive and Iontophoretic Transport through the Skin Polar Pathway

Peck

2013

Skin Pharmacol Physiol

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The purpose of the present article is to briefly recount the contributions of Prof. William I. Higuchi to the area of skin transport. These contributions include developing fundamental knowledge of the barrier properties of the stratum corneum, mechanisms of skin transport, concentration gradient across skin in topical drug applications that target the viable epidermal layer, and permeation enhancement by chemical and electrical means. The complex and changeable nature of the skin barrier makes it difficult to assess and characterize the critical parameters that influence skin permeation. The systematic and mechanistic approaches taken by Dr. Higuchi in studying these parameters provided fundamental knowledge in this area and had a measured and lasting influence upon this field of study. This article specifically reviews the validation and characterization of the polar permeation pathway, the mechanistic model of skin transport, the influence of the dermis on the target skin concentration concept, and iontophoretic transport across the polar pathway of skin including the effects of electroosmosis and electropermeabilization.

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Section: Iontophoretic Transport Across the Polar Pathwaymentioning

confidence: 55%

Section: Iontophoretic Transport Across the Polar Pathwaymentioning

confidence: 99%

Section: Iontophoretic Transport Across the Polar Pathwaymentioning

confidence: 99%

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Passive and Iontophoretic Transport through the Skin Polar Pathway

Peck

2013

Skin Pharmacol Physiol

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“…For the iontophoretic transport of a neutral permeant, the Peclet number (Pe i ) is determined from the enhancement factor (E v,i ) by (Peck et al, 1996):…”

Section: Theory and Equationsmentioning

confidence: 99%

Chemical method to enhance transungual transport and iontophoresis efficiency

Hao

Smith

2008

International Journal of Pharmaceutics

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Transungual transport is hindered by the inherent small effective pore size of the nail even when it is fully hydrated. The objectives of this study were to determine the effects of chemical enhancers thioglycolic acid (TGA), glycolic acid (GA), and urea (UR) on transungual transport and iontophoresis efficiency. In vitro passive and iontophoretic transport experiments of model permeants mannitol (MA), UR, and tetraethylammonium (TEA) ion across the fully hydrated, enhancer-treated and untreated human nail plates were performed in phosphate-buffered saline. The transport experiments consisted of several stages, alternating between passive and anodal iontophoretic transport at 0.1 mA. Nail water uptake experiments were conducted to determine the water content of the enhancer-treated nails. The effects of the enhancers on transungual electroosmosis were also evaluated. Nails treated with GA and UR did not show any transport enhancement. Treatment with TGA at 0.5 M enhanced passive and iontophoretic transungual transport of MA, UR, and TEA. Increasing the TGA concentration to 1.8 M did not further increase TEA iontophoresis efficiency. The effect of TGA on the nail plates was irreversible. The present study shows the possibility of using a chemical enhancer to reduce transport hindrance in the nail plate and thus enhance passive and iontophoretic transungual transport.

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“…These phenomena support the hypothesis that the mechanism of enhancement by IP was mainly caused by the convective flow rate. 17,18) Thus chemicals that had increased convective flow with US treatment showed synergistic effects in skin penetration with USϩIP.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Synergistic Skin Penetration by Sonophoresis and Iontophoresis

Hikima

Ohsumi

Shirouzu

et al. 2009

Biological & Pharmaceutical Bulletin

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Transdermal therapeutic systems have been developed by conceiving effective enhancement methods against the stratum corneum (SC) barrier function.1) Researchers have reported a number of chemical, biochemical, and physical enhancers that increase the skin flux of drugs by different mechanisms.2,3) These enhancers individually increase the flux in in vitro skin penetration and in vivo animal experiments, although their applications in humans are limited due to undesirable side effects. For safety, economic, and efficacy reasons, a combination of enhancers was proposed in several reports.4-6) Previously, we reported that the ultrasound (US) and iontophoresis (IP) combination (USϩIP) synergistically increased the penetration flux of a chemical with large molecular weight in vitro.7) It was clear that US increased the diffusivity of chemicals in the SC and that IP enhanced the movement of water through the SC.This study investigated the mechanism of the synergistic effects on skin penetration with USϩIP. We performed skin penetration experiments with US and IP using seven model chemicals with different electric charges and molecular weights in vitro. Moreover, the effects of electroosmosis during IP application were simulated assuming a bilayer [SC and viable skin (VS)] skin model. 8) We discuss the effects of an electric charge and molecular weight on the synergistic enhancement by USϩIP. Table 1. The molecular weight of the model chemicals used ranged from 100 to 1500 and, under those conditions, the SC controlled their skin penetration. 9) In this study, we especially paid attention to the molecular weight and electric charge of chemicals. MATERIALS AND METHODS MaterialsHydrogel Preparation After the model chemicals were dissolved in phosphate buffer 5 mM (pH 7.4), the buffer and hiviswako104 were thoroughly mixed. Then, triethylamine was added to adjust the gel pH to neutral. Each model chemical was maintained at a fixed concentration during the experiment, as listed in Table 1. Blank gel without a model chemical was also prepared as described above. The hydrogels were stored in a refrigerator at 4°C before use.In Vitro Skin Penetration Experiment Abdominal intact and stripped skin was excised from hairless mice. The stripped skin completely removed the SC from intact skin by adhesive tape (CT-24F, Nichiban Co., Ltd., Tokyo, Japan) stripping. The skin samples were mounted on a vertical penetration cell system (Vidrex Co., Ltd., Fukuoka, Japan) with two half moon-shaped diffusion areas (2 cm 2 ).10) The epidermis of the skin faced the receptor compartment (55 ml) that was filled with phosphate buffer solution (pH 7.4). The donor Mechanisms of Synergistic Skin Penetration by Sonophoresis and IontophoresisTomohiro HIKIMA,* Shinya OHSUMI, Kenta SHIROUZU, and Kakuji TOJO The mechanism of skin penetration enhancement by ultrasound under sonophoresis (US) or by an electrical field under iontophoresis (IP) was investigated using hairless mouse skin in vitro. The seven model chemicals with different molecular weights (...

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Quantitative Description of the Effect of Molecular Size upon Electroosmotic Flux Enhancement during Iontophoresis for a Synthetic Membrane and Human Epidermal Membrane

Cited by 42 publications

References 25 publications

Passive and Iontophoretic Transport through the Skin Polar Pathway

Passive and Iontophoretic Transport through the Skin Polar Pathway

Chemical method to enhance transungual transport and iontophoresis efficiency

Mechanisms of Synergistic Skin Penetration by Sonophoresis and Iontophoresis

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