scholarly journals Expression of drug transporters in the human skin: comparison in different species and models and its implication for drug development

ADMET & DMPK ◽  
2017 ◽  
Vol 5 (2) ◽  
pp. 75 ◽  
Author(s):  
Hanan Osman-Ponchet ◽  
Alexandre Gaborit ◽  
Jean-Michel Linget ◽  
Claire E. Wilson
Keyword(s):  
Human Skin ◽  
Drug Absorption ◽  
Transdermal Delivery ◽  
Drug Transporters ◽  
Drug Distribution ◽  
Skin Surface ◽  
Pharmacological Intervention ◽  
Novel Targets

<p class="ADMETabstracttext">It is clear that many drug transporters (both ABCs and SLCs) are present in the human skin. Different in vitro skin models can be used to investigate the role of drug transporters in the skin despite quantitative differences in expression profile across species. P-gp was shown to have an important influence on transdermal drug absorption in the skin and to function in “absorptive” transport, carrying substrate drugs from the skin surface to the dermis. This observation might be used to modulate drug distribution inside the skin. If drugs can be retained in the epidermis compartment by inhibition of the transporters, such property of the drug would be beneficial for treatment of dermatological diseases. Therefore, it might be feasible to control transdermal delivery of drugs to specific locations in the skin, by modulating the function of the transporters in the skin. We are at the dawn of an exciting period where drug transporters might be novel targets for improvement of drug delivery to the skin and for pharmacological intervention.</p>

scholarly journals The Use of Micro- and Nanocarriers for Resveratrol Delivery into and across the Skin in Different Skin Diseases—A Literature Review

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 451
Author(s):  
Beata Szulc-Musioł ◽  
Beata Sarecka-Hujar
Keyword(s):  
Transdermal Delivery ◽  
Bacterial Infections ◽  
Skin Diseases ◽  
Skin Surface ◽  
Non Invasive ◽  
Skin Abnormalities ◽  
Low Solubility ◽  
Active Substances ◽  
Poor Stability

In recent years, polyphenols have been extensively studied due to their antioxidant, anticancer, and anti-inflammatory properties. It has been shown that anthocyanins, flavonols, and flavan-3-ols play an important role in the prevention of bacterial infections, as well as vascular or skin diseases. Particularly, resveratrol, as a multi-potent agent, may prevent or mitigate the effects of oxidative stress. As the largest organ of the human body, skin is an extremely desirable target for the possible delivery of active substances. The transdermal route of administration of active compounds shows many advantages, including avoidance of gastrointestinal irritation and the first-pass effect. Moreover, it is non-invasive and can be self-administered. However, this delivery is limited, mainly due to the need to overpassing the stratum corneum, the possible decomposition of the substances in contact with the skin surface or in the deeper layers thereof. In addition, using resveratrol for topical and transdermal delivery faces the problems of its low solubility and poor stability. To overcome this, novel systems of delivery are being developed for the effective transport of resveratrol across the skin. Carriers in the micro and nano size were demonstrated to be more efficient for safe and faster topical and transdermal delivery of active substances. The present review aimed to discuss the role of resveratrol in the treatment of skin abnormalities with a special emphasis on technologies enhancing transdermal delivery of resveratrol.

scholarly journals Host/Malassezia Interaction: A Quantitative, Non-Invasive Method Profiling Oxylipin Production Associates Human Skin Eicosanoids with Malassezia

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 700
Author(s):  
Yohannes Abere Ambaw ◽  
Martin P. Pagac ◽  
Antony S. Irudayaswamy ◽  
Manfred Raida ◽  
Anne K. Bendt ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Immune System ◽  
Polyunsaturated Fatty Acids ◽  
Human Skin ◽  
Skin Surface ◽  
Lipid Mediators ◽  
Dependent Manner ◽  
Human Immune System ◽  
Plant Host

Malassezia are common components of human skin, and as the dominant human skin eukaryotic microbe, they take part in complex microbe–host interactions. Other phylogenetically related fungi (including within Ustilagomycotina) communicate with their plant host through bioactive oxygenated polyunsaturated fatty acids, generally known as oxylipins, by regulating the plant immune system to increase their virulence. Oxylipins are similar in structure and function to human eicosanoids, which modulate the human immune system. This study reports the development of a highly sensitive mass-spectrometry-based method to capture and quantify bioactive oxygenated polyunsaturated fatty acids from the human skin surface and in vitro Malassezia cultures. It confirms that Malassezia are capable of synthesizing eicosanoid-like lipid mediators in vitro in a species dependent manner, many of which are found on human skin. This method enables sensitive identification and quantification of bioactive lipid mediators from human skin that may be derived from metabolic pathways shared between skin and its microbial residents. This enables better cross-disciplinary and detailed studies to dissect the interaction between Malassezia and human skin, and to identify potential intervention points to promote or abrogate inflammation and to improve human skin health.

Insights in the molecular mechanisms of an azole stress adapted laboratory-generated Aspergillus fumigatus strain

2021 ◽  
Author(s):  
Marion Aruanno ◽  
Samantha Gozel ◽  
Isabelle Mouyna ◽  
Josie E Parker ◽  
Daniel Bachmann ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Aspergillus Fumigatus ◽  
Molecular Mechanisms ◽  
Drug Transporters ◽  
Major Facilitator Superfamily ◽  
Ergosterol Biosynthesis ◽  
Azole Resistance ◽  
Drug Transporter

Abstract Aspergillus fumigatus is the main cause of invasive aspergillosis, for which azole drugs are the first-line therapy. Emergence of pan-azole resistance among A. fumigatus is concerning and has been mainly attributed to mutations in the target gene (cyp51A). However, azole resistance may also result from other mutations (hmg1, hapE) or other adaptive mechanisms. We performed microevolution experiment exposing an A. fumigatus azole-susceptible strain (Ku80) to sub-minimal inhibitory concentration of voriconazole to analyze emergence of azole resistance. We obtained a strain with pan-azole resistance (Ku80R), which was partially reversible after drug relief, and without mutations in cyp51A, hmg1, and hapE. Transcriptomic analyses revealed overexpression of the transcription factor asg1, several ATP-binding cassette (ABC) and major facilitator superfamily transporters and genes of the ergosterol biosynthesis pathway in Ku80R. Sterol analysis showed a significant decrease of the ergosterol mass under voriconazole exposure in Ku80, but not in Ku80R. However, the proportion of the sterol compounds was similar between both strains. To further assess the role of transporters, we used the ABC transporter inhibitor milbemycine oxime (MLB). MLB inhibited transporter activity in both Ku80 and Ku80R and demonstrated some potentiating effect on azole activity. Criteria for synergism were reached for MLB and posaconazole against Ku80. Finally, deletion of asg1 revealed some role of this transcription factor in controlling drug transporter expression, but had no impact on azole susceptibility. This work provides further insight in mechanisms of azole stress adaptation and suggests that drug transporters inhibition may represent a novel therapeutic target. Lay Summary A pan-azole-resistant strain was generated in vitro, in which drug transporter overexpression was a major trait. Analyses suggested a role of the transporter inhibitor milbemycin oxime in inhibiting drug transporters and potentiating azole activity.

In Vitro Transdermal Delivery of a Melanotropic Peptide Through Human Skin

1990 ◽  
Vol 94 (4) ◽  
pp. 432-435 ◽  
Author(s):  
Brenda V Dawson ◽  
Mac E Hadley ◽  
Norman Levine ◽  
Kristie L Kreutzfeld ◽  
Scott Don ◽  
...  
Keyword(s):  
Human Skin ◽  
Transdermal Delivery

scholarly journals Contribution of Palmitic Acid to Epidermal Morphogenesis and Lipid Barrier Formation in Human Skin Equivalents

2019 ◽  
Vol 20 (23) ◽  
pp. 6069 ◽  
Author(s):  
Arnout Mieremet ◽  
Richard Helder ◽  
Andreea Nadaban ◽  
Gert Gooris ◽  
Walter Boiten ◽  
...  
Keyword(s):  
Palmitic Acid ◽  
Human Skin ◽  
De Novo ◽  
Skin Equivalents ◽  
Barrier Formation ◽  
Lipid Organization ◽  
Epidermal Morphogenesis ◽  
Lateral Organization

The outermost barrier layer of the skin is the stratum corneum (SC), which consists of corneocytes embedded in a lipid matrix. Biosynthesis of barrier lipids occurs de novo in the epidermis or is performed with externally derived lipids. Hence, in vitro developed human skin equivalents (HSEs) are developed with culture medium that is supplemented with free fatty acids (FFAs). Nevertheless, the lipid barrier formation in HSEs remains altered compared to native human skin (NHS). The aim of this study is to decipher the role of medium supplemented saturated FFA palmitic acid (PA) on morphogenesis and lipid barrier formation in HSEs. Therefore, HSEs were developed with 100% (25 μM), 10%, or 1% PA. In HSEs supplemented with reduced PA level, the early differentiation was delayed and epidermal activation was increased. Nevertheless, a similar SC lipid composition in all HSEs was detected. Additionally, the lipid organization was comparable for lamellar and lateral organization, irrespective of PA concentration. As compared to NHS, the level of monounsaturated lipids was increased and the FFA to ceramide ratio was drastically reduced in HSEs. This study describes the crucial role of PA in epidermal morphogenesis and elucidates the role of PA in lipid barrier formation of HSEs.

The migration of sebum and suint components along wool fibres of Merino sheep

1982 ◽  
Vol 33 (5) ◽  
pp. 817 ◽  
Author(s):  
JB Hay ◽  
SC Mills
Keyword(s):  
Human Skin ◽  
Skin Surface ◽  
Intradermal Injection ◽  
Direct Application ◽  
Wool Fibre ◽  
Merino Sheep ◽  
Wool Growth ◽  
Rapid Spread ◽  
Sheep Wool

It has been shown that isotopically labelled sheep wool wax is carried passively along the wool fibre as a band by growth of the wool, and that it does not flow along the fibre to any large extent during experiments of several months. This supports the view that the function of sebum, in mammals in general, is to protect the hair (wool) fibre and the condition of the coat, and contrasts with the reported rapid spread of sebum over the human skin surface. It also seems unlikely that wax lost from the fleece during exposure to rainfall is replenished with sebum freshly secreted onto the surface, since sebum does not migrate. Two methods were used to obtain labelled wax, direct application of labelled cholesterol to the skin surface and intradermal injection of labelled sebum substrate. Prior washing of the wool with detergent showed that wax already on the fibre was not the cause of the observed lack of flow of newly formed wax. Isotopically labelled suint components were also carried passively by wool growth. It is unlikely that wax is transported to any extent by suint in the wool; this is in contrast to the suggested role of sweat in facilitating the spread of sebum over the human skin surface. Some spreading of radioactive wax and suint bands was noted however, possibly because of diffusion and mechanical disturbance of the wool.

Transdermal delivery of insulin across human skin in vitro with 3D printed hollow microneedles

2021 ◽  
pp. 102891
Author(s):  
Iakovos Xenikakis ◽  
Konstantinos Tsongas ◽  
Emmanouil K. Tzimtzimis ◽  
Orestis Katsamenis ◽  
Efterpi Demiri ◽  
...  
Keyword(s):  
Human Skin ◽  
Transdermal Delivery ◽  
3D Printed ◽  
Hollow Microneedles
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