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

Abstract

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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Polyvinylpyrrolidone microneedles for localized delivery of sinomenine hydrochloride: preparation, release behavior of in vitro & in vivo, and penetration mechanism

“…Injections are more expensive and require professional training for administration (Wu et al, 2016;Arya et al, 2017). Transdermal drug delivery is an attractive alternative to oral administration or injection, and early studies confirmed that it could overcome the above-mentioned problems (Prausnitz & Langer, 2008;Romgens et al, 2015).…”

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