Investigation of transfollicular caffeine penetration using microdialysis on ex vivo porcine ear skin

Klein, Anna Lena; Lubda, Markus; Skov, Per Stahl; Vogt, Annika; Keck, Cornelia M.; Lademann, Jürgen; Darvin, Maxim E.; Hagen, Jörg von; Patzelt, Alexa

doi:10.1016/j.ejpb.2020.09.013

Cited by 16 publications

(13 citation statements)

References 37 publications

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“…To date, the term “fresh” is mainly used to clearly state that the skin and ears that were used for the presented skin study were not frozen and defrosted before use. The use of fresh ears can, therefore, mean that freshly obtained ears were directly used after they were collected from the slaughterhouse or at later time points, i.e., after storage for 24 to 72 h [ 5 , 6 , 8 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. A question that remains unanswered so far is if the storage time of the ears after slaughter affects the penetration efficacy of chemical compounds.…”

Section: Introductionmentioning

confidence: 99%

Assessing the Dermal Penetration Efficacy of Chemical Compounds with the Ex-Vivo Porcine Ear Model

et al. 2022

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(1) Background: The ex vivo porcine ear model is often used for the determination of the dermal penetration efficacy of chemical compounds. This study investigated the influence of the post-slaughter storage time of porcine ears on the dermal penetration efficacy of chemical compounds. (2) Methods: Six different formulations (curcumin and different fluorescent dyes in different vehicles and/or nanocarriers) were tested on ears that were (i) freshly obtained, (ii) stored for 24 or 48 h at 4 °C after slaughter before use and (iii) freshly frozen and defrosted 12 h before use. (3) Results: Results showed that porcine ears undergo post-mortem changes. The changes can be linked to rigor mortis and all other well-described phenomena that occur with carcasses after slaughter. The post-mortem changes modify the skin properties of the ears and affect the penetration efficacy. The onset of rigor mortis causes a decrease in the water-holding capacity of the ears, which leads to reduced penetration of chemical compounds. The water-holding capacity increases once the rigor is released and results in an increased penetration efficacy for chemical compounds. Despite different absolute penetration values, no differences in the ranking of penetration efficacies between the different formulations were observed between the differently aged ears. (4) Conclusions: All different types of ears can be regarded to be suitable for dermal penetration testing of chemical compounds. The transepidermal water loss (TEWL) and/or skin hydration of the ears were not correlated with the ex vivo penetration efficacy because both an impaired skin barrier and rigor mortis cause elevated skin hydration and TEWL values but an opposite penetration efficacy. Other additional values (for example, pH and/or autofluorescence of the skin) should, therefore, be used to select suitable and non-suitable skin areas for ex vivo penetration testing. Finally, data from this study confirmed that smartFilms and nanostructured lipid carriers (NLC) represent superior formulation strategies for efficient dermal and transdermal delivery of curcumin.

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Section: Introductionmentioning

confidence: 99%

Assessing the Dermal Penetration Efficacy of Chemical Compounds with the Ex-Vivo Porcine Ear Model

et al. 2022

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“…For this technique, a membrane is placed in the upper part of the dermis, constantly perfused and the perfusion medium is collected. The same material and general microdialysis setup as described by Klein et al [6] were used. In setup A, the mean depth of the membrane was 0.32 mm with an average standard deviation of 0.05 mm while in setup B, this depth was 0.30 mm and the mean standard deviation was 0.06 mm.…”

Section: Dermal Microdialysismentioning

confidence: 99%

“…After 46 h, the skin layers were separated to analyze how much caffeine penetrated. The separation of the skin layers (tape stripping, heat separation [31]), the homogenization and extraction were performed similarly as in the study by Klein et al [6]. The only difference between the protocols used was that in the present study, more tape strips had to be taken to remove the remaining formulation from the skin surface.…”

Section: Skin Separation Homogenization and Extraction After 46 Hmentioning

confidence: 99%

“…This becomes superior when it comes to the investigation of follicular and transfollicular penetration since the skin remains fixed on the cartilage. Klein et al [6] recently showed that microdialysis performed on porcine ear skin is capable to monitor the transfollicular penetration kinetics of caffeine. To investigate the effect of transfollicular penetration, caffeine can be used as an API since previous in vivo and ex vivo studies showed that the follicular penetration pathway influences the penetration kinetics of caffeine [24,25].…”

Section: Introductionmentioning

confidence: 99%

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Microdialysis on Ex Vivo Porcine Ear Skin Can Validly Study Dermal Penetration including the Fraction of Transfollicular Penetration—Demonstrated on Caffeine Nanocrystals

et al. 2021

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Common ex vivo methods for penetration investigations often fail to monitor transfollicular penetration appropriately. In the present investigation, the validity of dermal microdialysis on the ex vivo porcine ear skin to investigate penetration kinetics, including transfollicular penetration, was studied. In setup A, a caffeine nanocrystal formulation was compared to a non-particular caffeine gel formulation. In setup B, two caffeine nanocrystal formulations of different sizes (200 nm, 700 nm) were compared to each other. Microdialysis samples were collected for 46 h. After sampling, the skin layers were separated, homogenized, and caffeine was quantified in all samples. In setup A the area under the curve (AUC) after crystal gel formulation application was 12 times higher than after non-particular formulation application. Setup B showed an increased AUC of 42% in the microdialysis data when the 700 nm caffeine crystals were applied compared to the 200 nm crystals. The microdialysis data was supported by the separation, homogenization and extraction data. Microdialysis performed on ex vivo porcine ear skin is a novel experimental setup. It is of high interest for further investigations since it is able to also capture the impact of follicular and transfollicular penetration kinetics as no other ex vivo setup can.

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“…After overcoming the lipid-rich stratum corneum as the first line of defense, an effect can be elicited at a target either in the viable epidermis or further down in the dermis, whereby both layers are rich in aqueous content. For a penetration of active ingredients, the intracellular, intercellular, and follicular routes can be used for transport into or across the skin [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Lateral Dermal Penetration Is Dependent on the Lipophilicity of Active Ingredients

Lubda

Zander

Salazar

et al. 2022

Skin Pharmacol Physiol

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Introduction: With its large surface area skin facilitates a topical administration of active ingredients, and thus percutaneous delivery to a specific target site. Due to its high barrier function and different diffusion characteristics skin governs the efficacy of these active ingredients and a bioavailability in the epidermal and dermal tissue. Objective: In order to characterize the vertical and lateral movement of molecules into and inside the skin the diffusivity of active ingredients with different physico-chemical properties and their penetration ability in different dermal skin layers was investigated. Methods: A novel lateral dermal microdialysis (MD) penetration setup was used to compare the diffusion characteristics of active ingredients into superficial and deep implanted MD membranes in porcine skin. The corresponding membrane depth was determined via ultrasound and the active ingredients concentration via high-pressure liquid chromatography (HPLC) measurement. Results: The depth depended penetration of superficial and deep implanted MD membranes and the quantitative diffusivity of two active ingredients was compared. An experimental lateral MD setup was used to determine the influence of percutaneous skin penetration characteristics of an active ingredient with different lipophilic and hydrophilic characteristics. Therefore, hydrophilic caffeine and lipophilic LIP1, which have an identical molecular weight, but different lipophilic characteristics were tested for their penetration ability inside a propylene glycol (PG) and oleic acid (OA) formulation. Conclusion: The vertical and lateral penetration movement of caffeine was found to exceed that of LIP1 through the hydrophilic dermal environment. The findings of this study show that the lipophilicity of active ingredients influence the penetration movement and that skin enables a conical increasing lateral diffusivity and transdermal delivery.

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Investigation of transfollicular caffeine penetration using microdialysis on ex vivo porcine ear skin

Cited by 16 publications

References 37 publications

Assessing the Dermal Penetration Efficacy of Chemical Compounds with the Ex-Vivo Porcine Ear Model

Assessing the Dermal Penetration Efficacy of Chemical Compounds with the Ex-Vivo Porcine Ear Model

Microdialysis on Ex Vivo Porcine Ear Skin Can Validly Study Dermal Penetration including the Fraction of Transfollicular Penetration—Demonstrated on Caffeine Nanocrystals

Lateral Dermal Penetration Is Dependent on the Lipophilicity of Active Ingredients

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