scholarly journals N-Alkylmorpholines: Potent Dermal and Transdermal Skin Permeation Enhancers

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 64
Author(s):  
Kristýna Dvořáková ◽  
Petr Štěpánek ◽  
Jiřina Kroupová ◽  
Jarmila Zbytovská
Keyword(s):  
Mode Of Action ◽  
Drug Transport ◽  
Skin Permeation ◽  
Skin Barrier ◽  
Hydrocarbon Chain ◽  
Transepidermal Water Loss ◽  
Permeation Enhancers ◽  
Routes Of Administration ◽  
Dermal Delivery

Transdermal drug delivery is an attractive non-invasive method offering numerous advantages over the conventional routes of administration. The main obstacle to drug transport is, however, the powerful skin barrier that needs to be modulated, for example, by transdermal permeation enhancers. Unfortunately, there are still only a few enhancers showing optimum properties including low toxicity and reversibility of enhancing effects. For this reason, we investigated a series of new N-alkylmorpholines with various side chains as potential enhancers in an in vitro permeation study, using three model permeants (theophylline, indomethacin, diclofenac). Moreover, electrical impedance, transepidermal water loss, cellular toxicity and infrared spectroscopy measurements were applied to assess the effect of enhancers on skin integrity, reversibility, toxicity and enhancers’ mode of action, respectively. Our results showed a bell-shaped relationship between the enhancing activity and the hydrocarbon chain length of the N-alkylmorpholines, with the most efficient derivatives having 10–14 carbons for both transdermal and dermal delivery. These structures were even more potent than the unsaturated oleyl derivative. The best results were obtained for indomethacin, where particularly the C10-14 derivatives showed significantly stronger effects than the traditional enhancer Azone. Further experiments revealed reversibility in the enhancing effect, acceptable toxicity and a mode of action based predominantly on interactions with stratum corneum lipids.

scholarly journals Skin Barriers in Dermal Drug Delivery: Which Barriers Have to Be Overcome and How Can We Measure Them?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 684 ◽  
Author(s):  
Christian Gorzelanny ◽  
Christian Mess ◽  
Stefan W. Schneider ◽  
Volker Huck ◽  
Johanna M. Brandner
Keyword(s):  
Drug Delivery ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Multiphoton Microscopy ◽  
Skin Barrier ◽  
Barrier Properties ◽  
Transepidermal Water Loss ◽  
Hair Follicles

Although, drugs are required in the various skin compartments such as viable epidermis, dermis, or hair follicles, to efficiently treat skin diseases, drug delivery into and across the skin is still challenging. An improved understanding of skin barrier physiology is mandatory to optimize drug penetration and permeation. The various barriers of the skin have to be known in detail, which means methods are needed to measure their functionality and outside-in or inside-out passage of molecules through the various barriers. In this review, we summarize our current knowledge about mechanical barriers, i.e., stratum corneum and tight junctions, in interfollicular epidermis, hair follicles and glands. Furthermore, we discuss the barrier properties of the basement membrane and dermal blood vessels. Barrier alterations found in skin of patients with atopic dermatitis are described. Finally, we critically compare the up-to-date applicability of several physical, biochemical and microscopic methods such as transepidermal water loss, impedance spectroscopy, Raman spectroscopy, immunohistochemical stainings, optical coherence microscopy and multiphoton microscopy to distinctly address the different barriers and to measure permeation through these barriers in vitro and in vivo.

scholarly journals An Investigation of the Influence of PEG 400 and PEG-6-Caprylic/Capric Glycerides on Dermal Delivery of Niacinamide

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2907
Author(s):  
Yanling Zhang ◽  
Majella E. Lane ◽  
David J. Moore
Keyword(s):  
Skin Permeation ◽  
Ternary Systems ◽  
Pharmaceutical Products ◽  
Porcine Skin ◽  
Peg 400 ◽  
Skin Delivery ◽  
Dermal Delivery ◽  
Binary And Ternary Systems ◽  
Skin Retention

Polyethylene glycols (PEGs) and PEG derivatives are used in a range of cosmetic and pharmaceutical products. However, few studies have investigated the influence of PEGs and their related derivatives on skin permeation, especially when combined with other solvents. Previously, we reported niacinamide (NIA) skin permeation from a range of neat solvents including propylene glycol (PG), Transcutol® P (TC), dimethyl isosorbide (DMI), PEG 400 and PEG 600. In the present work, binary and ternary systems composed of PEGs or PEG derivatives combined with other solvents were investigated for skin delivery of NIA. In vitro finite dose studies were conducted (5 μL/cm2) in porcine skin over 24 h. Higher skin permeation of NIA was observed for all vehicles compared to PEG 400. However, overall permeation for the binary and ternary systems was comparatively low compared with results for PG, TC and DMI. Interestingly, values for percentage skin retention of NIA for PEG 400:DMI and PEG 400:TC were significantly higher than values for DMI, TC and PG (p < 0.05). The findings suggest that PEG 400 may be a useful component of formulations for the delivery of actives to the skin rather than through the skin. Future studies will expand the range of vehicles investigated and also look at skin absorption and residence time of PEG 400 compared to other solvents.

Influence of skin permeation enhancers on the transdermal delivery of palonosetron: An in vitro evaluation

2018 ◽  
Vol 16 (3) ◽  
pp. 192-197 ◽  
Author(s):  
Anroop B. Nair ◽  
Shery Jacob ◽  
Bandar E. Al-Dhubiab ◽  
Rakan Naser Alhumam
Keyword(s):  
Transdermal Delivery ◽  
Skin Permeation ◽  
Permeation Enhancers ◽  
In Vitro Evaluation

scholarly journals Transepidermal Water Loss Does Not Correlate with Skin Barrier Function In Vitro

2002 ◽  
Vol 118 (5) ◽  
pp. 871-875 ◽  
Author(s):  
Robert P. Chilcott ◽  
Christopher H. Dalton ◽  
Andrew J. Emmanuel ◽  
Ceri E. Allen ◽  
Simon T. Bradley
Keyword(s):  
Water Loss ◽  
Barrier Function ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Skin Barrier Function

Effect of Various Nonionic Surfactants Incorporated in Liposomes on Dermal Delivery of Hydrophilic Compound

2014 ◽  
Vol 1060 ◽  
pp. 12-16
Author(s):  
Worranan Rangsimawong ◽  
Praneet Opanasopit ◽  
Theerasak Rojanarata ◽  
Tanasait Ngawhirunpat
Keyword(s):  
Nonionic Surfactants ◽  
Skin Permeation ◽  
Physicochemical Characteristic ◽  
Skin Penetration ◽  
Tween 20 ◽  
Negative Surface ◽  
Negative Surface Charge ◽  
Dermal Delivery ◽  
Hydrophilic Compound

Various surfactants-containing vesicles have been widely used as a carrier in drug delivery to enhance skin penetration of encapsulated therapeutic agents. The purpose of this study was to investigate the effect of nonionic surfactants-containing liposome vesicles on the penetration of hydrophilic compounds through the porcine skin. Ultradeformable liposomes composed of phosphatidylcholine (PC), cholesterol (Chol) and various surfactants e.g. Tween 20, Labrasol and Gelucire 44/14) were prepared as NaFI carrier. The physicochemical characteristic of liposomes and in vitro skin penetration were investigated. The particle size of surfactant-containing liposome vesicles showed smaller particle sizes (36 to 54 nm) than conventional liposome (CLs) and had negative surface charge. The EE% and LE% order of surfactants incorporated in liposome formulations were: Labrasol liposomes (LALs) > Gelucire 44/14 liposomes (GELs) > Tween20 liposomes (TWLs) > CLs. The flux of NaFI from ultradeformable liposomes was significantly higher than from CLs. Among various liposomes, Labrasol containing ultradeformable liposomes showed the highest skin permeation in 24 h, and their flux was significantly higher (p < 0.05) than the flux of CLs. The result suggests that the surfactant-containing liposomes were small and deformable vesicles due to incorporating of an edge activators. In addition, surfactants could act as a penetration enhancer to promote dermal delivery of NaFI.

scholarly journals Oryza Ceramide®, a rice-derived extract consisting of glucosylceramides and β-sitosterol glucoside, improves facial skin dehydration in Japanese subjects

2021 ◽  
Vol 11 (8) ◽  
pp. 385
Author(s):  
Tsuyoshi Takara ◽  
Kazuo Yamamoto ◽  
Naoko Suzuki ◽  
Shinichiro Yamashita ◽  
Shin-ichiro Iio ◽  
...  
Keyword(s):  
Water Loss ◽  
Random Number Generator ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Controlled Study ◽  
Skin Barrier Function ◽  
Facial Skin ◽  
Double Blind ◽  
Hydrophobic Fraction

Background and objective: The ingestion of plant-derived glucosylceramides (GlcCer) has been reported to contribute to skin barrier function and hydration of the epidermis. b-sitosterol glucoside (BSG) colocalized with GlcCer in the rice hydrophobic fraction has been shown to increase ceramides in the stratum corneum in vitro. Although clinical studies demonstrated that GlcCer reduced transepidermal water loss (TEWL), the contribution of BSG to epidermal dehydration when applied with GlcCer remains unknown. Therefore, we herein conducted a clinical trial on the effects of a rice-derived mixed fraction of GlcCer and BSG (Oryza Ceramide®) on TEWL and other skin parameters. Methods: A randomized, double-blind, placebo-controlled study design was used. Oryza Ceramide® (type PCD, 40 mg daily) containing 1.2 mg of GlcCer and 40 mg of BSG was used as the active sample. We enrolled 44 healthy Japanese women with epidermal dehydration. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. Capsules containing the active sample or placebo were administered for 12 weeks between August and December 2020. Cheek TEWL after 12 weeks was assessed as the primary outcome, and TEWL on a different part of the skin and various skin parameters, including epidermal moisture, pigmentation, pores, and elasticity, were measured before and after 4, 8, and 12 weeks of the intervention. Blood, urine, and body parameters were also examined to evaluate safety.Results: Forty-four subjects completed the trial, and the per protocol set comprised 22 each in the active and placebo groups. Cheek TEWL significantly reduced after the Oryza Ceramide® intervention for 4 and 12 weeks. Among the secondary outcomes examined, lip moisture (12 weeks) and visible pore number (4 weeks) were improved by Oryza Ceramide®. Laboratory tests revealed no abnormalities to suggest any adverse effects of Oryza Ceramide®.Conclusions: Oryza Ceramide® (40 mg/day) consisting of GlcCer and BSG improved facial TEWL, lip moisture, and visible pores, and these effects may be attributed to increases in epidermal ceramides. The combination of rice GlcCer and BSG appears to be beneficial for improving facial skin conditions.Trial Registration: UMIN-CTR: UMIN000041295Foundation: The study was funded by Oryza Oil & Fat Chemical Co., Ltd. and Aichi Prefectural Subsidies for Research and Development of Creative Products in 2020.Keywords: rice; glucosylceramide; β-sitosterol glucoside; trans epidermal water loss; pore 

scholarly journals Partially Hydrolysed Whey-Based Infant Formula Improves Skin Barrier Function

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3113
Author(s):  
Sébastien Holvoet ◽  
Sophie Nutten ◽  
Lénaïck Dupuis ◽  
Dominique Donnicola ◽  
Tristan Bourdeau ◽  
...  
Keyword(s):  
Barrier Function ◽  
Protein Hydrolysate ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Skin Barrier Function ◽  
Primary Keratinocytes ◽  
Total Ige ◽  
Expression Of Genes ◽  
Human Primary Keratinocytes

Specific partially hydrolysed whey-based infant formulas (pHF-W) have been shown to decrease the risk of atopic dermatitis (AD) in infants. Historically, AD has been associated primarily with milk allergy; however, defective skin barrier function can be a primary cause of AD. We aimed to ascertain whether oral supplementation with pHF-W can improve skin barrier function. The effect of pHF-W was assessed on transepidermal water loss (TEWL) and antibody productions in mice epicutaneously exposed to Aspergillus fumigatus. Human primary keratinocytes were stimulated in vitro, and the expression of genes related to skin barrier function was measured. Supplementation with pHF-W in neonatal mice led to a significant decrease in TEWL and total IgE, but not in allergen-specific antibody levels. The whey hydrolysate was sufficient to decrease both TEWL and total IgE. Aquaporin-3 gene expression, linked with skin hydration, was modulated in the skin of mice and human primary keratinocytes following protein hydrolysate exposure. Skin barrier improvement may be an additional mechanism by which pHF-W may potentially reduce the risk of AD development in infants. Further human studies are warranted to confirm the clinical efficacy of these observations.

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