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

• Published in: Journal of the mechanical behavior of biomedical materials 2015-10, Vol.50, p.215-222
• Main Authors: Römgens, Anne M., Bader, Dan L., Bouwstra, Joke A., Baaijens, Frank P.T., Oomens, Cees W.J.
• Format: Article
• Language: English
• Subjects: Adult; Biological Transport; Dermis - metabolism; Diffusion; Diffusion coefficient; Drug Administration Routes; Epidermis - metabolism; Female; Finite Element Analysis; Fluorescence Recovery After Photobleaching; Fluorescent recovery after photobleaching; Human skin; Humans; Macromolecular Substances - administration & dosage; Macromolecular Substances - chemistry; Macromolecular Substances - metabolism; Middle Aged; Molecular Weight; Scanning microphotolysis; Targeted drug delivery
• ISSN: 1751-6161; 1878-0180
• DOI: 10.1016/j.jmbbm.2015.06.019

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 500kDa using a combination of fluorescent recovery after photobleaching experiments and finite element analysis. The diffusion coefficient was significantly higher for 40kDa than 500kDa dextran, with median values of 23 and 9µm2/s in the dermis, respectively. The values only marginally varied within and between papillary and reticular dermis. For the 40kDa 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. •The diffusion coefficient was determined at various locations in the human skin.•Diffusion coefficients only slightly varied between different locations in the skin.•The diffusion coefficient was dependent on the molecular weight of the molecule.