Electroperturbation of the human skin barrier in vitro (I): the influence of current density on the thermal behaviour of skin impedance

The topical delivery of bromelain as an anti-inflammatory solution for skin inflammation has attracted the attention of researchers. Due to the skin barrier issue, a new method was designed for the effective delivery of specific doses of bromelain to the desired action sites. A niosome was selected as a novel and practical transdermal vehicle for the delivery of bromelain to inflamed sites. In this regard, a lipopolysaccharide (LPS)-induced human skin fibroblast (HSF1184) cell line was assembled in-vitro as a simulated model. The levels of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α), the two immune-modulatory regulators of cell responses to inflammation, were measured to determine the response towards the niosome-encapsulated bromelain treatment. The results showed that the niosome-encapsulated bromelain significantly reduced the levels of IL-6 and TNF-α compared to the non-encapsulated bromelain, the vehicle (niosome) and the control.

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P24 Iontophoresis of a model peptide across human skin in vitro: effects of iontophoresis protocol, pH and ionic strength on peptide flux and skin impedance

Journal of Controlled Release ◽

10.1016/0168-3659(94)90106-6 ◽

1994 ◽

Vol 29 (3) ◽

pp. 396-397

Author(s):

W.H.M.Craane-van Hinsberg ◽

L. Bax ◽

N.H.M. Flinterman ◽

J. Verhoef ◽

H.E. Junginger ◽

...

Keyword(s):

Ionic Strength ◽

Human Skin ◽

Skin Impedance ◽

Model Peptide ◽

In Vitro Effects

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Investigating Human Skin Barrier Lipids with In Vitro Skin Models

Cosmetic Lipids and the Skin Barrier - Cosmetic Science and Technology ◽

10.1201/b14036-6 ◽

2001 ◽

pp. 121-147

Author(s):

Annie Black ◽

Odile Damour ◽

Kordula Schlotmann

Keyword(s):

Human Skin ◽

Skin Barrier

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P256 electroperturbation of the human skin barrier in vitro: effects on stratum corneum resistance, capacitance, lipid ordering and ultrastructure

European Journal of Pharmaceutical Sciences ◽

10.1016/0928-0987(94)90429-4 ◽

1994 ◽

Vol 2 (1-2) ◽

pp. 182

Author(s):

W.H.M. Craane-van Hinsberg ◽

F. Spies ◽

G.S. Gooris ◽

J.A. Bouwstra ◽

J.C. Verhoef ◽

...

Keyword(s):

Stratum Corneum ◽

Human Skin ◽

Skin Barrier ◽

In Vitro Effects

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Multitargeted Approach for the Optimization of Morphogenesis and Barrier Formation in Human Skin Equivalents

International Journal of Molecular Sciences ◽

10.3390/ijms22115790 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5790

Author(s):

Arnout Mieremet ◽

Richard W. J. Helder ◽

Andreea Nadaban ◽

Walter A. Boiten ◽

Gert S. Gooris ◽

...

Keyword(s):

Human Skin ◽

Three Dimensional ◽

Skin Barrier ◽

Collagen Matrix ◽

Optimization Approach ◽

Skin Equivalents ◽

Barrier Formation ◽

Epidermal Morphogenesis

In vitro skin tissue engineering is challenging due to the manifold differences between the in vivo and in vitro conditions. Yet, three-dimensional (3D) human skin equivalents (HSEs) are able to mimic native human skin in many fundamental aspects. However, the epidermal lipid barrier formation, which is essential for the functionality of the skin barrier, remains compromised. Recently, HSEs with an improved lipid barrier formation were generated by (i) incorporating chitosan in the dermal collagen matrix, (ii) reducing the external oxygen level to 3%, and (iii) inhibiting the liver X receptor (LXR). In this study, we aimed to determine the synergic effects in full-thickness models (FTMs) with combinations of these factors as single-, double-, and triple-targeted optimization approaches. The collagen–chitosan FTM supplemented with the LXR inhibitor showed improved epidermal morphogenesis, an enhanced lipid composition, and a better lipid organization. Importantly, barrier functionality was improved in the corresponding approach. In conclusion, our leading optimization approach substantially improved the epidermal morphogenesis, barrier formation, and functionality in the FTM, which therefore better resembled native human skin.

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Iontophoretic Transdermal Delivery of Human Growth Hormone (hGH) and the Combination Effect of a New Type Microneedle, Tappy Tok Tok®

Pharmaceutics ◽

10.3390/pharmaceutics10030153 ◽

2018 ◽

Vol 10 (3) ◽

pp. 153 ◽

Cited By ~ 5

Author(s):

Gyubin Noh ◽

Taekwang Keum ◽

Jo-Eun Seo ◽

Santosh Bashyal ◽

Nyeon-Sik Eum ◽

...

Keyword(s):

Growth Hormone ◽

Human Growth Hormone ◽

Current Density ◽

Transdermal Delivery ◽

Recombinant Human Growth Hormone ◽

Skin Barrier ◽

Human Growth ◽

Blue Staining ◽

Citrate Buffer

Transdermal drug administration presents several advantages and it is therefore favorable as an alternative drug delivery route. However, transdermal delivery of biopharmaceutical drugs is made difficult by the skin barrier. Microneedle application and iontophoresis are strategies which can be used to overcome this barrier. Therefore, recombinant human growth hormone (rhGH) was used as a model macromolecular drug and was transdermally delivered using microneedle application and iontophoresis. Methylene blue staining, stereomicroscopy and scanning electron microscope (SEM) imaging were used to characterize the microchannels produced. To optimize the iontophoresis protocol, the effects of molecular charge and current density on transdermal delivery were evaluated in an in vitro permeation study using excised rat skin tissues. Using the optimized iontophoresis protocol, the combination effects of iontophoretic delivery via microchannels were evaluated in three different experimental designs. The flux obtained with anodal iontophoresis in citrate buffer was approximately 10-fold higher that that with cathodal iontophoresis in phosphate buffered saline (PBS). Flux also increased with current density in anodal iontophoresis. The combination of iontophoresis and microneedle application produced higher flux than single application. These results suggest that anodal iontophoresis with higher current density enhances the permeation of macromolecules through microchannels created by microneedles. In conclusion, the combination of iontophoresis and microneedles is a potential strategy for the enhancement of transdermal delivery of macromolecular drugs.

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Electroperturbation of the human skin barrier in vitro: II. Effects on stratum corneum lipid ordering and ultrastructure

Microscopy Research and Technique ◽

10.1002/(sici)1097-0029(19970501)37:3<200::aid-jemt5>3.0.co;2-r ◽

1997 ◽

Vol 37 (3) ◽

pp. 200-213 ◽

Cited By ~ 20

Author(s):

Ine W.H.M. Craane-Van Hinsberg ◽

J. Coos Verhoef ◽

Ferry Spies ◽

Joke A. Bouwstra ◽

Gert S. Gooris ◽

...

Keyword(s):

Stratum Corneum ◽

Human Skin ◽

Skin Barrier ◽

Stratum Corneum Lipid

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Modulation of the Lipid Profile of Reconstructed Skin Substitutes after Essential Fatty Acid Supplementation Affects Testosterone Permeability

Cells ◽

10.3390/cells8101142 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1142 ◽

Cited By ~ 4

Author(s):

Mélissa Simard ◽

Pierre Julien ◽

Julie Fradette ◽

Roxane Pouliot

Keyword(s):

Benzoic Acid ◽

Human Skin ◽

Barrier Function ◽

Percutaneous Absorption ◽

Skin Barrier ◽

Skin Barrier Function ◽

Skin Permeability ◽

Skin Substitutes ◽

Reconstructed Human Skin

Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate whether PUFAs, alpha-linolenic acid (ALA, n-3 PUFA) and linoleic acid (LA, n-6 PUFA), could enhance the impermeability of a three-dimensional reconstructed human skin model, skin substitutes were produced according to the self-assembly method using culture media supplemented with either 10 μM ALA or 10 μM LA. The impact of PUFAs on skin permeability was studied by using a Franz cell diffusion system to assess the percutaneous absorption of testosterone and benzoic acid. Our findings showed that ALA supplementation induced a decrease in the absorption of testosterone, while LA supplementation did not significantly influence the penetration of testosterone and benzoic acid under present experimental conditions. Both ALA and LA were incorporated into phospholipids of the skin substitutes, resulting in an increase in n-3 total PUFAs or n-6 total PUFAs. Collectively, these results revealed the under-estimated impact of n-3 PUFA supplementation as well as the importance of the n-6 to n-3 ratio on the formation of the skin barrier of in vitro reconstructed human skin models.

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Optimization and Evaluation of the In Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs through Strat-M® Membrane

Pharmaceutics ◽

10.3390/pharmaceutics13081305 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1305

Author(s):

Bartłomiej Milanowski ◽

Hanna Wosicka-Frąckowiak ◽

Eliza Główka ◽

Małgorzata Sosnowska ◽

Stanisław Woźny ◽

...

Keyword(s):

Human Skin ◽

Skin Barrier ◽

Pharmaceutical Products ◽

Topical Formulations ◽

In Vitro Permeation ◽

Diffusion Characteristics ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Spray Formulation

Pharmaceutical products containing non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed topical formulations used for analgesic and antirheumatic properties. These drugs must overcome the skin barrier to cause a therapeutic effect. Human skin has been widely used as a model to study in vitro drug diffusion and permeation, however, it suffers from many limitations. Therefore, to perform in vitro permeation test (IVPT), we used a Strat-M® membrane with diffusion characteristics well-correlated to human skin. This study’s objective was to optimize the IVPT conditions using Plackett–Burman experimental design for bio-predictive evaluation of the in vitro permeation rates of five non-steroidal anti-inflammatory drugs (diclofenac, etofenamate, ibuprofen, ketoprofen, naproxen) across Strat-M® membrane from commercial topical formulations. The Plackett–Burman factorial design was used to screen the effect of seven factors in eight runs with one additional center point. This tool allowed us to set the sensitive and discriminative IVPT final conditions that can appropriately characterize the NSAIDs formulations. The permeation rate of etofenamate (ETF) across the Strat-M® membrane was 1.7–14.8 times faster than other NSAIDs from selected semisolids but 1.6 times slower than the ETF spray formulation.

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