title: Depth-resolved characterization of diffusion properties within and across minimally-perturbed skin layers.
abstract: 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 (70 kDa and 2 MDa 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).
authors.affiliation: Delivery of Drugs and Genes Group (D²G²), Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Raphael
authors.forename: Stefano C
authors.initials: SC
authors.lastname: Meliga
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Chen
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
authors.forename: Christopher
authors.initials: C
authors.lastname: Flaim
authors.forename: Mark A F
authors.initials: MA
authors.lastname: Kendall
mesh_terms: D000465:Algorithms; D000818:Animals; D003692:Delayed-Action Preparations; D020405:Dermis / Q000378:metabolism; D003911:Dextrans; D004058:Diffusion; D016503:Drug Delivery Systems; D004817:Epidermis / Q000378:metabolism; D005453:Fluorescence; D005456:Fluorescent Dyes; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D066298:In Vitro Techniques; D051379:Mice; D018613:Microscopy, Confocal; D012235:Rhodamines; D012869:Skin Absorption / Q000502:physiology*
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D005456:Fluorescent Dyes; D012235:Rhodamines; C051311:rhodamine dextran