Depth-resolved characterization of diffusion properties within and across minimally-perturbed skin layers

We examine by both experimental and computational means the diffusion of macromolecules through the skin strata (both the epidermis and dermis). Using mouse skin as a test case, we present a novel high-resolution technique to characterize the diffusion properties of heterogeneous biomaterials using...

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Bibliographic Details
Published in:Journal of controlled release 2013-03, Vol.166 (2), p.87-94
Main Authors: Raphael, Anthony P., Meliga, Stefano C., Chen, Xianfeng, Fernando, Germain J.P., Flaim, Christopher, Kendall, Mark A.F.
Format: Article
Language:English
Subjects:
3D confocal microscopy
Algorithms
Animals
Antigen-presenting cells
biocompatible materials
Delayed-Action Preparations
Dermis
Dermis - metabolism
Dextrans
Diffusion
diffusivity
Drug Delivery Systems
Epidermis - metabolism
Fluorescence
Fluorescent Dyes
image analysis
Image processing
Image Processing, Computer-Assisted
Imaging, Three-Dimensional
In Vitro Techniques
Macromolecular diffusion
Mice
Microneedles
Microscopy, Confocal
Rhodamine dextran
Rhodamines
Skin Absorption - physiology
vaccines
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Summary:We examine by both experimental and computational means the diffusion of macromolecules through the skin strata (both the epidermis and dermis). Using mouse skin as a test case, we present a novel high-resolution technique to characterize the diffusion properties of heterogeneous biomaterials using 3D imaging of fluorescent probes, precisely-deposited in minimally-perturbed in vivo skin layers. We find the diffusivity of the delivered macromolecules (70kDa and 2MDa rhodamine-dextrans) low within the packed cellular arrangement of the epidermis, while gradually increasing (by ~an order of magnitude) through the dermis — as pores in the fibrillar network enlarge from the papillary to the reticular dermis. Our experimental and computational approaches for investigating the diffusion through skin strata help in the assessment and optimization of controlled delivery of drugs (e.g. vaccines) to specific sites (e.g. antigen presenting cells). By imaging fluorescent macromolecules (dextrans) precisely deposited into skin strata with a microprojection array, we find that diffusivity is low in the viable epidermis and increases in the dermis. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2012.12.010