Visualization of in vitro percutaneous penetration of mercuric chloride; transport through intercellular space versus cellular uptake through desmosomes

Boddé, Harry E.; Brink, I. van den; Koerten, H. K.; Haan, F. H. N. de

doi:10.1016/0168-3659(91)90114-s

Cited by 111 publications

(64 citation statements)

References 10 publications

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“…These regions may represent areas where local skin resistance is lower than that of adjacent tissue. Similarly, previous studies have identified localized regions of high current density (i.e., sites of small ion transport) during iontophoresis [11][12][13] and have also reported molecular transport that was intercellular during passive [7][8][9][10] and iontophoretic 10,14,15 exposures. Unlike previous studies, the localized sites of transport observed in this study were not associated with appendages.…”

Section: Discussionmentioning

confidence: 99%

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Imaging Regions of Transport Across Human Stratum Corneum during High-Voltage and Low-Voltage Exposures

Prausnitz

Gimm

Guy

et al. 1996

Journal of Pharmaceutical Sciences

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0 Scanning confocal fluorescence microscopy was used to image localized regions of calcein transport across human stratum corneum during constant low-voltage (iontophoresis) and pulsed highvoltage exposures. Following an electrical protocol, imaging revealed regions of fluorescence which were interpreted as sites where transport of a fluorescent probe (calcein) into the stratum corneum had taken place. Electrically-assisted transport of calcein, whether enhanced by iontophoresis or high-voltage pulsing, appears to occur through intercellular and, to some extent, transcellular pathways into localized regions of stratum corneum that are not associated with appendages. Uniquely associated with the highest voltage pulses used (300 V across the skin) was the appearance of small, brightly fluorescent areas containing nonfluorescent interiors, i.e., fluorescent "rings". We present evidence which suggests that the dark interiors represent sites through which transport occurred during pulsing, but where calcein was no longer present at the time of imaging. Transport of charged microspheres into the stratum corneum was also observed.

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Section: Discussionmentioning

confidence: 99%

“…Under passive conditions, drugs are believed to diffuse across the stratum corneum following a tortuous intercellular route. [7][8][9][10] During iontophoresis, pathways for small ions apparently exist within sweat ducts and hair follicles. 9,[11][12][13] Iontophoretic transport of drugs may also occur through the bulk of stratum corneum.…”

Section: Introductionmentioning

confidence: 99%

Imaging Regions of Transport Across Human Stratum Corneum during High-Voltage and Low-Voltage Exposures

Prausnitz

Gimm

Guy

et al. 1996

Journal of Pharmaceutical Sciences

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“…Experimental evidence suggests the intercellular route to be predominantly followed under normal circumstances (Bodde et al 1991;Heisig et al 1996). The diffusional pathlength is, therefore, much longer than the simple thickness of the SC (∼20 µm) and has been estimated to be as long as 500 µm.…”

Section: Introductionmentioning

confidence: 99%

Transdermal Delivery of Carvedilol Containing Glycyrrhizin and Chitosan as Permeation Enhancers: Biochemical, Biophysical, Microscopic and Pharmacodynamic Evaluation

2008

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The present study was aimed at unveiling the influence of glycyrrhizin and chitosan on rat epidermis and to correlate these effects with percutaneous permeation characteristics of carvedilol. The permeation of carvedilol across excised rat epidermis was significantly higher ( p < 0.05) when glycyrrhizin, chitosan, or glycyrrhizin-chitosan mixture was used as a donor vehicle as compared to propylene glycol:ethanol (7:3) mixture. Epidermis obtained after 12 hr treatment of viable rat skin with a glycyrrhizin-chitosan mixture showed significantly higher ( p < 0.05) permeability to carvedilol as compared to that after treatment with glycyrrhizin or chitosan alone. Further, the application of patches containing glycyrrhizin-chitosan mixture resulted in sustained release of carvedilol, which was able to control the hypertension in deoxycorticosterone acetate induced hypertensive rats through 28 hr. Estimation of microconstituents in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and triglycerides after treatment with glycyrrhizin-chitosan mixture. This was manifested in altered lipid and protein-specific thermotropic transitions. Further, increase in intercellular space, disordered lipid structure and corneocyte detachment as observed in SEM and TEM suggests great potential of glycyrrhizin for use as a percutaneous permeation enhancer.

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“…The penetrant was indeed localized to the expanded interstitial spaces, an observation to be confirmed in later experiments using a modified approach and different compounds [15,16]. Despite these experimental observations that underpinned conclusions based on sophisticated modelling, the most persuasive evidence for the tortuous pathway involved an investigation that linked the principal barrier function of skin, namely to retard the loss of tissue water from inside the body, to fully quantifiable measurements of SC lipid biophysics.…”

Section: The Path Through the Scmentioning

confidence: 99%

Skin - ‘That Unfakeable Young Surface'

Guy

2013

Skin Pharmacol Physiol

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The 20- to 25-year period from the mid-1960s to the early 1990s represents, in many ways, a ‘golden era' in the understanding of skin barrier function, percutaneous penetration and (trans)dermal drug delivery. From the ground-breaking mechanistic work of Scheuplein and Blank, and the ‘gold standard' in vivo skin absorption experiments of Feldmann and Maibach, through the unravelling of the stratum corneum's structural and physicochemical characteristics that make it such an incredible feat of bioengineering, to the elegant biophysical and modelling studies of Potts, Francoeur and many others, the idea of administering drugs rationally to treat both local and systemic diseases was transformed from something close to the ravings of a lunatic to the reality of significant therapeutic and commercial success. This short article attempts to pick out some of the highlights along the way from the viewpoint of an interested observer and occasional participant in the ‘action'.

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Visualization of in vitro percutaneous penetration of mercuric chloride; transport through intercellular space versus cellular uptake through desmosomes

Cited by 111 publications

References 10 publications

Imaging Regions of Transport Across Human Stratum Corneum during High-Voltage and Low-Voltage Exposures

Imaging Regions of Transport Across Human Stratum Corneum during High-Voltage and Low-Voltage Exposures

Transdermal Delivery of Carvedilol Containing Glycyrrhizin and Chitosan as Permeation Enhancers: Biochemical, Biophysical, Microscopic and Pharmacodynamic Evaluation

Skin - ‘That Unfakeable Young Surface'

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