Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: Using a pig-ear model in vitro

Pažoureková, Silvia; Hojerová, Jarmila; Klímová, Zuzana; Lucová, Marianna

doi:10.1016/j.fct.2013.07.025

Cited by 32 publications

(13 citation statements)

References 63 publications

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“…After 8 h of contact with the rabbit skin, which is a good model for human skin, 60% of MP was found across the skin whereas ethyl‐ and propylparaben reached a value of 40% and 20%, respectively (Pedersen et al, ). This can be as a result of the greatest MP penetration into the skin despite its the lowest lipophilicity (El Hussein et al, ; Pažoureková et al, ). A few studies on dermal absorptions in volunteers reveal that parabens were found in the skin and blood in their native form (Ishiwatari et al, ; Janjua et al, , ; Sandanger et al, ) because of insufficient hydrolysis by skin esterase.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in individuals with damaged or impaired barrier caused by skin disorders, injury, wounds, waxing, shaving, etc. the risk of paraben dermal absorption may be enhanced (Pažoureková et al, ). According to Mowad (), accumulation of MP in the skin may contribute to higher risk of sensitization and can induce allergic contact dermatitis.…”

Section: Discussionmentioning

confidence: 99%

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Methylparaben‐induced decrease in collagen production and viability of cultured human dermal fibroblasts

Majewska

Zaręba

Surażyński

et al. 2017

J of Applied Toxicology

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Parabens owing to their many advantageous properties are widely applied in cosmetics, food products and pharmaceuticals. However, recent research results have shown that they possess the ability to accumulate in the human body and exert many adverse effects. In this study, the impact of methylparaben (MP) as the most frequently used preservative in cosmetics, on human dermal fibroblasts and collagen production was evaluated. In cells treated with 0.01, 0.03 and 0.05% MP a dose-dependent decrease in collagen biosynthesis was revealed, which was positively correlated with the activity of prolidase responsible for the recovery of proline. Consequently, the concentration of total collagen secreted into the medium was markedly diminished. A similar reduction in expression of the major skin collagen type I at both the protein and mRNA level as well as collagen type III and VI at the mRNA level was also detected. The decrease in the collagen level may result not only from the reduced synthesis but also increased degradation owing to MP-induced activation of pro-MMP-2 (72 kDa). The increase in activity of MMP-2 (66 kDa) was accompanied by a reduction in the inhibitory activity of TIMP-2. In addition, an inhibitory effect of MP on cell survival and proliferation was revealed in this study. The increased expression and nuclear translocation of caspase-3 as well as increased Bax and decreased Bcl-2 expression may suggest MP-induced cell apoptosis. In summary, we have provided new data on the adverse effects of methylparaben on human dermal fibroblasts and the main structural protein of the skin. Further studies on the mechanisms responsible for its action are in progress. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Methylparaben‐induced decrease in collagen production and viability of cultured human dermal fibroblasts

Majewska

Zaręba

Surażyński

et al. 2017

J of Applied Toxicology

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Section: Preclinical Pharmacokinetic Evaluationsmentioning

confidence: 99%

“…Transepidermal water loss from the skin or electrical conductivity measurements across the skin are useful for detection of skin damage, physical injury, or pathological conditions. The toxicity of the drug or formulation in the skin also may be investigated (Ashtikar et al, 2013;Pažoureková et al, 2013;Oliveira et al, 2014;Guth et al, 2015).Pharmacokinetic evaluations of a transdermal delivery system are essential to determine the in vivo behavior of the drug administered by the skin route because in vitro studies cannot reproduce the complexity of biological systems, such as metabolism, distribution, and elimination. The contribution of skin absorption by different pathways, such as the epidermis or skin appendages, is also important and may be characterized during the preclinical pharmacokinetic studies (Godin, Touitou, 2007;Farahmand, Maibach, 2009).…”

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confidence: 99%

Evaluation of skin absorption of drugs from topical and transdermal formulations

Ruela

Perissinato

Lino

et al. 2016

Braz. J. Pharm. Sci.

216

135

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The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed. Uniterms:Skin absorption/effects/study. Skin absorption/topical formulations. Skin absorption/ transdermal formulations. Skin absorptions/enhancers. INTRODUCTIONTopical and transdermal drug delivery systems have shown significant advantages in clinical practice for drug targeting to the action site in the body; this has reduced the systemic side effects. The administration of drugs by through the skin is also performed to achieve controlled or prolonged drug delivery, and this route can be explored as an alternative to the oral route. The oral route shows some limitations for drugs with irregular absorption in the gastrointestinal tract and low bioavailability and for drugs with increased first pass metabolism and short plasma halflife times (Barry, 2001;Wokovich et al., 2006;Prausnitz, Langer, 2009;Alexander et al., 2012).Many drug products applied to the skin surface may penetrate to some extent into the skin layers, where their effects are expected. This is the case for topical formulations for treatment of skin disorders such as acne and cutaneous inflammatory diseases that include dermatitis, erythematous lupus, and psoriasis. On the other hand, transdermal formulations release drugs that permeate through the skin and enter the systemic circulation. Transdermal therapy must ensure that significant concentrations of the drug are absorbed to reach effective plasma concentrations. Permeation of drugs is targeted in some cases to body regions close to the action site, where a regional effect is expected, e.g., in the muscles, blood vessels, and articulations. In this way, the term "cutaneous absorption" is properly used to characterize the sum of the amounts of drug that penetrate and permeate the skin (Barry, 2001;El Maghraby, Barry;Willi...

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“…Therefore, in vitro studies using frozen skin may not provide full information on dermal absorption of compounds that are transported through metabolic pathways or that undergo biotransformation inside skin . Significant biotransformation of tested compounds such as parabens , testosterone or catechines occurs in fresh (viable) skin owing to the presence of enzymes from the major biotransformation pathways . Sintov observed faster penetration rates for caffeine and diclofenac in frozen skin that he attributed to alterations of skin barrier functions during freezing .…”

Section: Introductionmentioning

confidence: 99%

Formulation of survival acceptor medium able to maintain the viability of skin explants over in vitro dermal experiments

Tarnowska

Briançon

Azevedo

et al. 2019

Intern J of Cosmetic Sci

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OBJECTIVE: In vitro assessments of skin absorption of xenobiotics are essential for toxicological evaluations and bioavailability studies of cosmetic and pharmaceutical ingredients. Since skin metabolism can greatly contribute to xenobiotic absorption, experiments need to be performed with skin explants kept viable in suitable survival media. Existing protocols for non-viable skin are modified to consider those conditions. The objective was to design a survival medium used as an acceptor fluid in Franz cells for testing cutaneous penetration of hydrophilic or lipophilic molecules. Their metabolism inside skin may be investigated under the same conditions. The determining factors involved in survival mechanisms in vitro are discussed. The consequences of short-term skin preservation at 4°C were also evaluated. METHODS: The metabolic activity of fresh skin samples mounted in Franz cells was studied by measurement of lactate release over 24 h in order to assess the impacts of pH, buffering, osmolality, ionic strength, initial glucose supply and the addition of ethanol or non-ionic surfactant in the acceptor part of Franz cells. CONCLUSION: Survival media must maintain physiological pH (>5.5) be isotonic with skin cells (300 mOsm kg À1 ) and contain at least 0.5 g L À1 glucose. Several compositions able to preserve skin metabolism are reported. Storage of skin explants overnight at 4°C impairs skin metabolic activity. The present work provides guidelines for designing survival media according to constraints related to the scientific requirements of the experiments.

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Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: Using a pig-ear model in vitro

Cited by 32 publications

References 63 publications

Methylparaben‐induced decrease in collagen production and viability of cultured human dermal fibroblasts

Methylparaben‐induced decrease in collagen production and viability of cultured human dermal fibroblasts

Evaluation of skin absorption of drugs from topical and transdermal formulations

Formulation of survival acceptor medium able to maintain the viability of skin explants over in vitro dermal experiments

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