Journal
JOURNAL OF CONTROLLED RELEASE
Volume 118, Issue 1, Pages 18-26Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2006.10.022
Keywords
transdermal drug delivery; analysis of skin microdialysis data; depth profile of skin permeability sink; cutaneous blood vessels distribution; area distribution of skin microvasculature
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We analysed quantitatively blood microvessels distribution in normal skin. We conclude that the segmental area of blood vessels peaks approximately 0.1 mm below the skin surface, where the upper cutaneous blood plexus resides. Total blood vessels area then decreases quasi-exponentially to a depth of approx. -0.75 mm, with a decay length of -0.1 mm, which is site and skin condition dependent, but at greater depths the decrease is approx. 6-times less steep. The corresponding permeability sink exhibits a similar, but superficially steeper, depth-profile. The lateral localisation of superficial blood vessels is such that ensures maximum diffusion from and into the capillaries, which affects transdermal drug delivery: each hairpin-like loop is in the centre of a papilla that corresponds to a cluster of comeocytes surrounded by main diffusion pathways. The aggregate area of blood vessels in the skin is >= 2.5-fold greater than total organ surface area under normal physiological conditions. The molecules diffusing through the skin barrier are thus largely cleared in outermost 20% of the organ, which may create a drug concentration maximum in the dermis, if clearance increases significantly with time. Skin microdialysis data are therefore extremely sensitive to cutaneous blood flow (distribution) and sampling. Skin microvasculature and its distribution must consequently be considered in all topical or transdermal drug transport studies, for example, by including suitably formulated clearance term into generalised diffusion equation. (c) 2006 Elsevier B.V. All rights reserved.
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