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Structure and Function of Human Skin
by: John Eminescu
Human skin is a uniquely engineered organ
that permits terrestrial life by regulating heat and water loss
from the body whilst preventing the ingress of noxious chemicals
or microorganisms. It is also the largest organ of the humen
body, providing around 10% of the body mass of an average
person, and it covers an average area of 1.7 m2. Whilst such a
large and easily accessible organ apparently offers ideal and
multiple sites to administer therapeutic agents for both local
and systemic actions, human skun is a highly efficient
self-repairing barrier designed to keep ‘the insides in and the
outside out’.
Human skin is a highly complex organ though in many transdermal
drug delivery studies it is often regarded somewhat
simplistically as merely a physical barrier. In vivo, skin is in
a process of continual regeneration, it has immunological and
histological responses to assault (as would be the case if an
exogenous chemical, such as a drug, were applied to the surface)
and is metabolically active. Due to experimental and ethical
difficulties, most transdermal drug delivery studies tend to
utilize skin ex vivo (in vitro) which inherently reduces some of
the above complexity – regeneration stops, immune responses
cease and metabolic activity is usually lost in these studies.
However, it should always be borne in mind that data obtained
from excised skin may not translate directly to the in-vivo
situation.
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For the purpose of transdermal drug delivery, we can examine the
structure and function of humen skin categorized into four main
layers :
• the innermost subcutaneous fat layer (hypodermis)
• the overlying dermis
• the viable epidermis
• the outermost layer of the tissue (a non-viable epidermal
layer) the stratum corneum.
The subcutaneous fat layer
The subcutaneous fat layer, or hypodermis, bridges between the
overlying dermis and the underlying body constituents. In most
areas of the body this layer is relatively thick, typically in
the order of several millimeters. However, there are areas of
the body in which the subcutaneous fat layer is absent, such as
the eyelids. This layer of adipose tissue principally serves to
insulate the body and to provide mechanical protection against
physical shock. The subcutaneous fatty layer can also provide a
readily available supply of high-energy molecules, whilst the
principal blood vessels and nerves are carried to the skin in
this layer.
The dermis
The dermis (or corium) is typically 3–5 mm thick and is the
major component of human skin. It is composed of a network of
connective tissue, predominantly collagen fibrils providing
support and elastic tissue providing flexibility, embedded in a
mucopolysaccharide gel (Wilkes et al.,1973). In terms of transdermal drug delivery, this layer is often viewed as
essentially gelled water, and thus provides a minimal barrier to
the delivery of most polar drugs, although the dermal barrier
may be significant when delivering highly lipophilic molecules.
The dermis has numerous structures embedded within it; blood and
lymphatic vessels, nerve endings, pilosebaceous units (hair
follicles and sebaceous glands), and sweat glands (eccrine and
apocrine).
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The epidermis
The epidermis is itself a complex multiply layered membrane, yet varies in
thickness from around 0.06 mm on the eyelids to around 0.8 mm on the
load-bearing palms and soles of the feet. The epidermis contains no blood
vessels and hence nutrients and waste products must diffuse across the dermo-epidermal
layer in order to maintain tissue integrity.
Likewise, molecules permeating across the epidermis must cross the dermo-epidermal
layer in order to be cleared into the systemic circulation. The epidermis
contains four histologically distinct layers which, from the inside to the
outside, are the stratum germinativum, stratum spinosum, stratum granulosum
and the stratum corneum.
A fifth layer, the stratum lucidum, is sometimes described but is more
usually considered to be the lower layers of the stratum corneum. The
stratum corneum, comprising anucleate (dead) cells, provides the main
barrier to transdermal delivery of drugs and hence is often treated as a
separate membrane by workers within the field. The term ‘viable epidermis’
is often used to describe the underlying layers, although the viability of
cells within, for example, the stratum granulosum is questionable as the
cell components degrade during differentiation.
Epidermal enzyme systems
As well as the cellular component of the epidermis, the tissue contains many
drug-metabolizing enzymes. Histochemical and immunohistochemical
methodologies suggest that the majority of these are localized in the
epidermis, sebaceous glands and hair follicles. Although present at
relatively small quantities in comparison to the liver, they do allow
metabolic activity that can effectively reduce the bioavailability of
topically applied medicaments; a common misconception is that the skin is an
‘inert’ tissue. Indeed, most phase 1 (e.g. oxidation, reduction, hydrolysis)
and phase 2 (e.g. methylation, glucuronidation) reactions can occur within
the skin, though these tend to be at
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