title: Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery.
abstract: Delivering 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 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.
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: a.m.romgens@tue.nl.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Römgens
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; Faculty of Health Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Bader
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Frank P T
authors.initials: FP
authors.lastname: Baaijens
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Cees W J
authors.initials: CW
authors.lastname: Oomens
mesh_terms: D000328:Adult; D001692:Biological Transport; D020405:Dermis / Q000378:metabolism*; D004058:Diffusion; D004333:Drug Administration Routes; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D020342:Finite Element Analysis; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D008875:Middle Aged; D008970:Molecular Weight
chemical_list: D046911:Macromolecular Substances
keywords: Diffusion coefficient; Fluorescent recovery after photobleaching; Human skin; Scanning microphotolysis; Targeted drug delivery