Biomedical Engineering Reference
In-Depth Information
and nonpolar lipids, polar lipids are more crucial to skin barrier integrity. Because of
its highly organized structure, the SC is the major permeability barrier to any external
material and is regarded as the rate-limiting factor in penetration of therapeutic agents
utilizing skin as a route. The ability of various agents to interact with the intercellular
lipid therefore dictates the degree to which absorption is enhanced.
12.1.2.2 Viable Epidermis
The viable epidermis contains multiple layers of keratinocytes at various stages of
differentiation. The basal layer contains actively dividing cells, which travel upward
successively to form the spinous, granular, and clear layers. As part of this process,
the cells steadily lose their nuclei and undertake changes in composition. The role of
the viable epidermis in skin barrier function is mainly related to the intercellular lipid
channels and continuous partitioning phenomena. Normally, when applied, drugs can
partition from layer to layer, depending on their solubility after the drug starts to dif-
fuse through the SC. Several other cells (e.g., melanocytes, Langerhans cells, dendritic
T cells, epidermotropic lymphocytes, and merkel cells) are available throughout the
viable epidermis, which also contains a variety of active catabolic enzymes, for exam-
ple, esterases, phosphatases, proteases, nucleotidases, and lipases. Lipid catabolic
enzymes like acid lipase, phospholipase, sphingomyelinase, and steroid sulfatase,
although mainly concentrated in the SC and granulosum, have been demonstrated
throughout the epidermal layers. Lipase and sphingomyelinase were localized primar-
ily to intercellular domains in the SC [3] . Although the basal and spinous layers are
rich in phospholipids, as the cells differentiate during their journey to the surface, the
phospholipid content decreases and the sphingolipid (glucosylceramide and ceramide)
and cholesterol content simultaneously increases.
12.1.2.3 Dermis and Hypodermis
The dermis is largely acellular and is rich in blood vessels, lymphatic vessels, and
nerve endings. A widespread network of dermal capillaries connects to the systemic
circulation, with considerable horizontal branching from the arterioles and venules in
the papillary dermis, to form plexuses and to supply capillaries to hair follicles and
glands. Dermal lymphatic vessels help to drain surplus extracellular fluid and clear
antigenic materials. The elasticity of the dermis is attributed to a network of protein
fibers, including collagen (type I and III) and elastin, which are surrounded in an
amorphous glycosaminoglycan ground substance. The dermis also contains scattered
fibroblasts, macrophages, mast cells, and leukocytes. Hair follicles, sebaceous glands,
and sweat glands found in the dermis and subcutis might serve as additional, albeit
fairly limited, pathways for drug absorption.
In some cases, for example, hair follicles might act as target sites for drug delivery.
12.1.3  Penetration Pathways Through the Skin
A compound may use two different ways to penetrate normal intact human skin: the
transappendageal pathway and the transepidermal pathway. The transappendageal
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