Skin – anatomy and function
The skin is the body’s largest and primary protective organ. The skin covers the body’s entire external surface and serves as a first-order physical barrier against the environment. Functions: temperature regulation and protection against UV light, injury, pathogens, microorganisms and toxins. Moreover, the skin plays a role in immunologic surveillance, sensory perception, control of insensible fluid loss, and homeostasis. One of the most important function of the skin is transport route for cosmetic active substances and it is very significant fact for the cosmetic industry.
The skin has three layers: the epidermis, the dermis and the subcutaneous layer.
The epidermis is composed of keratinized, stratified squamous epithelium. The epidermis is made of four or five layers of epithelial cells, depending on its location in the body. These layers are: the stratum basale, stratum spinosum, stratum granulosum, and stratum corneum – listed from deep to superficial. Skin fifth layer, called the stratum lucidum, is located between the stratum corneum and the stratum granulosum. This layer is only on the palms of the hands and the soles of the feet. The cells in all of the layers except the stratum basale are called keratinocytes. The keratinocytes in the stratum corneum are dead, called corneocytes, and regularly slough away, being replaced by cells from the deeper layers.
The dermis is the inner layer that includes blood and lymph vessels, nerves, and other structures, such as hair follicles, sweat and sebaceous glands. The dermis has two layers of connective tissue that compose an interconnected mesh of elastin and collagenous fibers, produced by fibroblasts.
The subcutaneous layer is a layer below the dermis and serves to connect the skin to the underlying fascia (fibrous tissue) of the bones and muscles. The hypodermis consists of well-vascularized, loose, areolar connective tissue and adipose tissue.
Skin permeation routes
The stratum corneum is the main barrier to percutaneous adsorption of the most of the actives ingredients used in cosmetic products. There are three skin permeation routes:
- Intercellular route – the transepidermal delivery of active substances can be achieved via the intercellular cement lipids, in between corneocytes. Typical route of substance penetration for natural compounds lipophilic.
- Transcellular route – the transepidermal delivery of active substances can be achieved through the corneocytes. Typical route of substance penetration for insoluble in intercellular cement hydrophilic substances.
- Transfollicular route – the active substances penetrate the skin through the its appendages such as: the sweat glands, the sebaceous glands, and the hair follicles. This route for permeation flux of active substances is small, because skin appendages represent only 0.1% of the total surface of the human skin.
The main diffusion route for active substances through the skin is the intercellular route. It is impossible to circumvent the barrier made of the lipid matrix and deliver an active substance through the transcellular route only. An active ingredients must always pass the intercellular lipophilic matrix which is the major determinant of the skin permeation process. Due to this fact, the skin permeation routes such as: transcellular and transfollicular are an alternative pathway to the intact epidermis. The major route of skin permeation is through the stratum corneum. Most active substances penetrate the skin through the hydrophobic intercellular cement, so lipophilic compounds can easily pass the outer layer, but the transport of hydrophilic compounds (especially the ionized) is significantly limited. The route through the skin appendages enables permeation of charged molecules and large polar compounds (e.g. peptides).
Mechanism of skin permeation
Mechanism of skin permeation consist of several steps involved in the penetration of an active substance from its vehicle or the base formulation into the skin. The stages of the processes in their order of performance are:
- dissolution of the active ingredient in the vehicle or the base formulation and down to the outer skin surface,
- diffusion of the active ingredient within the vehicle or the base formulation and down to the skin surface,
- distribution of the active ingredient between the vehicle or the base formulation and the lipids in the stratum corneum,
- diffusion within the stratum corneum,
- distribution between the lipophilic stratum corneum and the deeper hydrophilic and vivid epidermal layers,
- diffusion through the hydrophilic epidermal layers and into the dermis.
Factors affecting transdermal permeability
There are several factors which influence the efficacy of active substances permeation through the skin. They can be classified into main four groups:
- properties of the diffusing substance, (solubility in lipids and water, oil/water partition coefficient, polarity, charge, degree of dissociation, and molecular mass),
- properties of base, (penetrating properties, content of auxiliary substances – permeation promoters, content of surfactants, formation of occlusion, pH),
- biological factors (skin health, skin thickness, age, blood flow, and hydration of the stratum corneum),
- physical factors, e.g. temperature, climate, massage, electrophoresis, or microneedling, which favour skin permeation.
The main and basic barrier for active compounds penetrating through the skin is the stratum corneum, which has lipophilic character and compact structure – this two factors limits the penetration of particles into the skin. The physicochemical properties of the stratum corneum can be modified by the use of transepidermal transport promoters. The transepidermal transport promotes can reversibly change the structure of intercellular cement and improve permeability of stratum corneum. Its properties also have a significant impact on the ability of a substance to penetrate physicochemical parameters, such as lipophilicity or molecular size and structure. Tests carried out in recent years have allowed for increased efficiency cosmetics and better absorption of active compounds through the skin. The penetration of active substances through the skin is one of the most important factors determining the effectiveness of cosmetics action.
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