Improved Method for Determining Partition and Diffusion Coefficients in Human Dermis

Ibrahim, Rania; Kasting, Gerald B.

doi:10.1002/jps.22216

Cited by 23 publications

(23 citation statements)

References 24 publications

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“…In addition, the difference may be reinforced by possible damage due to heat separation of the epidermis used by Cornelissen and co-workers (Cornelissen et al, 2008). The values for the dermis were comparable with the wide range of previously reported diffusion coefficient for relative small molecules in human dermis (190-300 Da) (Ibrahim and Kasting, 2010;Xing et al, 2009). In the current study, the diffusion coefficient of the epidermis was found to be lower than in the dermis for 40 kDa dextran molecules, as reported in previous studies on murine and human skin (Raphael et al, 2013;Xing et al, 2009).…”

Section: Discussionsupporting

confidence: 84%

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Römgens

Bader

Bouwstra

et al. 2015

Journal of the Mechanical Behavior of Biomedical Materials

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Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery, Journal of the Mechanical Behavior of Biomedical Materials, http://dx.doi. org/10.1016/j.jmbbm.2015.06.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractDelivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the outer layer of the skin in therapeutic amounts, but also macromolecules. To provide insight into the administration of these molecules into the skin, the aim of this study was to assess the transport of macromolecules within and between its various layers. The diffusion coefficients in the epidermis and several locations in the papillary and reticular dermis were determined for fluorescein dextran of 40 and 500 kDa using a combination of fluorescent recovery after photobleaching experiments and finite element analysis. The diffusion coefficient was significantly higher for 40 kDa than 500 kDa dextran, with median values of 23 and 9 µm 2 /s in the dermis, respectively. The values only marginally varied within and between the papillary and reticular dermis. For the 40 kDa dextran, the diffusion coefficient in the epidermis was twice as low as in the dermis layers. The adopted method may be used for other macromolecules, which are of interest for dermal and transdermal drug delivery. The knowledge about diffusion in the skin is useful to optimize (trans)dermal drug delivery systems to target specific layers or cells in the human skin.

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Section: Discussionsupporting

confidence: 84%

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Römgens

Bader

Bouwstra

et al. 2015

Journal of the Mechanical Behavior of Biomedical Materials

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“…26) However, the transdermal delivery of resveratrol was very limited under the conditions in this study, possibly due to the binding to albumin, 27) which is present in large quantities in the dermis. 28) The time courses of the distribution ratio between the dermis and epidermis of the polyphenols differed between MESL and MEK; rapid distribution from the vehicle to the epidermis but slower distribution from the epidermis to the dermis were observed in MESL, while both distribution processes seemed to be slow in MEK. Although it was not elucidated, hydration of the stratum corneum as mentioned above and the dermalepidermal basement membrane zone barrier, such as basement membrane, might be responsible for this difference in distribution.…”

Section: Discussionmentioning

confidence: 98%

Efficient Delivery and Distribution in Skin of Chlorogenic Acid and Resveratrol Induced by Microemulsion Using Sucrose Laurate

et al. 2014

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To achieve efficient skin delivery of polyphenols, we prepared a novel oil-in-water (o/w)-type microemulsion (MESL) using sucrose laurate as a surfactant and ethanol, isopropyl myristate and water as other components. We examined its usefulness by in vitro studies on skin delivery of chlorogenic acid and resveratrol as hydrophilic and hydrophobic polyphenols using Yucatan micropig skin, and also examined the difference in the distribution of these polyphenols in skin. MESL significantly improved skin incorporation of these polyphenols at all time points examined (6, 20, 40 h) in the epidermis and at 20 and 40 h in the dermis, compared with the microemulsion using Tween 80 as a surfactant component (MEK), although the solubilization capacity of MESL was lower than that of MEK. Using MESL, the incorporation amount in the dermis of each polyphenol increased with time, while the amount in the epidermis was almost constant during the time examined. Incorporation efficiencies into skin of chlorogenic acid and resveratrol induced by MESL at 40 h after application were about 6-fold and 19-fold higher in the epidermis and 3.5-fold and 15-fold higher in the dermis, respectively, than those by MEK. The increase was more prominent for resveratrol. Hydrophilic chlorogenic acid was distributed slightly more in the epidermis, while hydrophobic and smaller-molecularweight resveratrol was mainly distributed in the dermis. These findings suggest that MESL could be a promising vehicle for the efficient skin delivery of chlorogenic acid and resveratrol, especially for resveratrol to the dermis.Key words microemulsion; sucrose laurate; polyphenol; chlorogenic acid; resveratrol; skin Polyphenols are well-known antioxidants and have been shown to have a wide range of therapeutic potential, such as via anti-inflammatory and anticancer activities, as well as protective effects against cardiovascular and neurodegenerative diseases.1,2) Polyphenols can also be applied to skin for topical effects, including protection against UV-induced oxidative damage (photoaging), skin cancer prevention and skin care 3,4) ; however, the penetration of polyphenols into skin is often limited due to their poor solubility in both aqueous and organic solvents as well as relatively high molecular weight. There is thus a need for enhancement systems to be introduced for their topical application.Microemulsions consist of an aqueous phase, an oil phase, a surfactant and a co-surfactant component, which are thermodynamically stable and have been shown to have high solubilization capacity and to facilitate the skin incorporation of both hydrophilic and lipophilic drugs. 5,6) In previous studies, we revealed that microemulsions using polyoxyethylene sorbitan monooleate (Tween 80) as a surfactant component are useful for the intradermal delivery of polyphenols, such as quercetin, genistein and chlorogenic acid. 7-9) However, the incorporation efficiencies of these polyphenols from the vehicle into skin were low. In another study, we also revealed that an anionic su...

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“…Binding of 14 C-parathion in a 2% (w/v) BSA solution in PBS was determined by equilibrium dialysis as previously described (Ibrahim and Kasting, 2010). The 2% (w/v) level was chosen as it is the approximate average concentration of albumin in human dermis (Kretsos et al, 2008).…”

Section: Protein Bindingmentioning

confidence: 99%

“…Soluble proteins present in the dermis can migrate slowly through the tissue. This potential movement necessitates a careful choice of the in vitro methodology employed in the measurement of dermis transport parameters of highly protein-bound solutes (Ibrahim and Kasting, 2010). In particular, if soluble proteins migrate into the donor compartment of a side-by-side diffusion cell experiment, and the test permeant binds to these proteins, then an artificially low permeability would be obtained (Ibrahim and Kasting, 2010;Kretsos et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…This potential movement necessitates a careful choice of the in vitro methodology employed in the measurement of dermis transport parameters of highly protein-bound solutes (Ibrahim and Kasting, 2010). In particular, if soluble proteins migrate into the donor compartment of a side-by-side diffusion cell experiment, and the test permeant binds to these proteins, then an artificially low permeability would be obtained (Ibrahim and Kasting, 2010;Kretsos et al, 2008). In a previous study we showed that exclusion of soluble proteins from the donor compartment of side-by-side diffusion cells had a significant effect on the measured transport parameters for a highly protein-bound solute, diclofenac.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Partitioning and diffusion of parathion in human dermis

Ibrahim

Kasting

2012

International Journal of Pharmaceutics

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Improved Method for Determining Partition and Diffusion Coefficients in Human Dermis

Cited by 23 publications

References 24 publications

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Efficient Delivery and Distribution in Skin of Chlorogenic Acid and Resveratrol Induced by Microemulsion Using Sucrose Laurate

Partitioning and diffusion of parathion in human dermis

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