Reflections on the OECD guidelines for in vitro skin absorption studies

Hopf, Nancy B.; Champmartin, Catherine; Schenk, Linda; Berthet, Aurélie; Chedik, Lisa; Plessis, Jeanetta du; Franken, Anja; Frasch, F.; Gaskin, Sharyn; Johanson, Gunnar; Julander, Anneli; Kasting, Gerald B.; Kilo, Sonja; Filon, Francesca Larese; Marquet, Fabrice; Midander, Klara; Reale, Elena; Bunge, Annette L.

doi:10.1016/j.yrtph.2020.104752

Cited by 35 publications

(39 citation statements)

References 75 publications

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“…), the type of vehicle, type of skin, and type of application (for example, with or without massage) [1][2][3][4]. Today, different in vitro, ex vivo, and in vivo methods are available for the testing of the dermal penetration efficacy, where the most often used method is in vitro testing with Franz diffusion cells [5]. Testing the dermal penetration with Franz diffusion cells is tedious work and requires experienced and careful handling.…”

Section: Introductionmentioning

confidence: 99%

Influence of Massage and Skin Hydration on Dermal Penetration Efficacy of Nile Red from Petroleum Jelly—An Unexpected Outcome

et al. 2021

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The study aimed at comparing the influence of direct and indirect skin hydration as well as massage on the dermal penetration efficacy of active compounds. Nile red was used as a lipophilic drug surrogate and was incorporated into Vaseline (petroleum jelly). The formulation was applied with and without massage onto either dry skin or pre-hydrated, moist skin. It was expected that the occlusive properties of Vaseline in combination with massage and enhanced skin hydration would cause a superposition of penetration-enhancing effects, which should lead to a tremendous increase in the dermal penetration efficacy of the lipophilic drug surrogate. Results obtained were diametral to the expectations, and various reasons were identified for causing the effect observed. Firstly, it was found that Vaseline undergoes syneresis after topical application. The expulsed mineral oil forms a film on top of the skin, and parts of it penetrate into the skin. The lipophilic drug surrogate, which is dissolved in the mineral oil, enters the skin with the mineral oil, i.e., via a solvent drag mechanism. Secondly, it was found that massage squeezes the skin and causes the expulsion of water from deeper layers of the SC. The expulsed water can act as a water barrier that prevents the penetration of lipophilic compounds and promotes the penetration of hydrophilic compounds. Based on the data, it is concluded that dermal penetration is a complex process that cannot only be explained by Fick’s law. It is composed of at least three different mechanisms. The first mechanism is the penetration of active ingredients with their solvents into the skin (convection, solvent drag), the second mechanism is the penetration of the active ingredient via passive diffusion, and the third mechanism can involve local penetration phenomena, e.g., the formation of liquid menisci and particle-associated penetration enhancement, which occur upon the evaporation of water and/or other ingredients from the formulation on top of the skin.

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Section: Introductionmentioning

confidence: 99%

Influence of Massage and Skin Hydration on Dermal Penetration Efficacy of Nile Red from Petroleum Jelly—An Unexpected Outcome

et al. 2021

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“…Due to the wide range of methods available, careful consideration should be given to determine the best appropriate approach for a particular study. Whatever test approach is employed, the results should be validated with reference substances showing comparable results to published values 72 . In general, there is a growing demand for a sustainable approach that involving biodegradable biopolymers, notably in biomedical applications.…”

Section: Future Directions and Prospectsmentioning

confidence: 96%

“…Whatever test approach is employed, the results should be validated with reference substances showing comparable results to published values. 72 In general, there is a growing demand for a sustainable approach that involving biodegradable biopolymers, notably in biomedical applications. The worldwide market for biopolymers is anticipated to approach $27.9 billion by 2025, with the pectin market is predicted to grow to $1.5 billion by 2025, from $1 billion in 2019.…”

Section: Future Directions and Prospectsmentioning

confidence: 99%

Investigations of pectin nanostructures for enhanced percutaneous delivery of fusidic acid

Bostanudin

Arafat

Tan

et al. 2022

J of Applied Polymer Sci

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The study aims to formulate and characterize nanoformulations produced from amphipathically-modified pectin containing fusidic acid, making clear the importance of nanocarrier amphipathicity in boosting drug permeation through the skin. For this purpose, the amphipathically-modified pectin (GBE-PEC) fabrication was achieved following glycidol butyl ether modification via the nucleophilic substitution S N 2 reaction, which was then characterized using thermal analysis, spectroscopic, and chromatographic tools. The materials were subsequently converted into spherical nanostructures (NSs) (size 250-290 nm; zeta potential À25 to À34 mV) via a nanoprecipitation in situ cross-linking approach, demonstrating low viscosity and good colloidal stability under pH 4 conditions. The encapsulated fusidic acid (loading degree 14.9%) was released from GBE-PEC NSs in a more controlled fashion, with release profiles best characterized by the Higuchi model. Interactions with HaCaT cells in vitro demonstrated no apparent cytotoxicity at application relevant conditions, with efficient cellular absorption as evidenced by flow cytometry analysis. Using Franz diffusion cells, GBE-PEC NSs had a 2-fold greater penetration rate through the Strat-M ® membrane than the native pectin NSs. Overall, the study has introduced new insights into the design, fabrication, characterization, and tremendous potential of NSs formulated from GBE-PEC for percutaneous delivery of poorly penetrating actives, which merit further analysis.

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“…Diffusion cells were jacketed in a recirculating water bath at 37 °C during the experiment to ensure that the skin temperature did not fall below 32 °C. 29 Samples (200 μL) were taken from the receptor compartment at 15, 30 and 60 min and then hourly until 8 h. Equal volume of receptor fluid (0.9% NaCl) was used to replenish the sampled amount. All experiments were conducted at least in triplicate.…”

Section: Skin Permeation Experimentsmentioning

confidence: 99%

“…Steady state was not achieved in the experimental timeframe for most experiments; hence, permeability coefficient (Kp) and lag time were not determined. 29 Statistical tests were performed using SPSS (IBM SPSS statistics 24, Sydney, New South Wales, Australia) with student's t-test used for statistical comparisons between groups.…”

Section: Permeation Parametersmentioning

confidence: 99%

The role of formulation co‐ingredients in skin and glove barrier protection against organophosphate insecticides

Tefera

Gaskin

Thredgold

et al. 2021

Pest Management Science

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BACKGROUND: Commercially formulated pesticide products are complex mixtures of one or more active ingredients and several co-ingredients. However, the modifying effect of co-ingredients on skin uptake and glove barrier protection has been poorly studied. The aim of this study was to understand the role of formulation co-ingredients in skin and glove barrier protection performance against organophosphate insecticides. RESULTS: We adapted standard in vitro diffusion cell methods to test permeation kinetics of two commonly used organophosphate insecticides: dimethoate and omethoate. For spray dilutions, dimethoate and omethoate did not reach breakthrough glove permeation rate (1 ∼g•cm −2 •min −1 ) and no or little skin permeation was observed for up to 8 h, regardless of formulation. For exposure conditions involving highly concentrated products, significant differences in glove permeation were observed between different formulations of dimethoate (about 1.5-fold, P < 0.05) and of omethoate (184-fold, P < 0.001). In contrast, no difference (P > 0.05) was observed between formulations in terms of skin permeation.CONCLUSION: These results suggest that co-ingredients play a critical role in glove barrier protection against undiluted organophosphate insecticides, whereas their influence on skin uptake was insignificant within the exposure time tested. This implies that dermal exposure risk may vary between handling different formulated products of the same active ingredient hence recommending a common glove material for different formulations of the same chemical without careful consideration of co-ingredients and their permeation properties may not necessarily be appropriate.

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Reflections on the OECD guidelines for in vitro skin absorption studies

Cited by 35 publications

References 75 publications

Influence of Massage and Skin Hydration on Dermal Penetration Efficacy of Nile Red from Petroleum Jelly—An Unexpected Outcome

Influence of Massage and Skin Hydration on Dermal Penetration Efficacy of Nile Red from Petroleum Jelly—An Unexpected Outcome

Investigations of pectin nanostructures for enhanced percutaneous delivery of fusidic acid

The role of formulation co‐ingredients in skin and glove barrier protection against organophosphate insecticides

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