14.2

Skin: As a Target Organ

Human skin is composed of dermis and epidermis layers. The outermost layer of the

skin, stratum corneum, is responsible for protection from the hazardous environment

by forming a barrier. The mechanism for penetration of actives could be by the sweat

duct, by the hair follicles, or in between the appendages of the stratum corneum

(Barry 2001). The follicles of the skin occupy around 0.1% of the surface area

(Scheuplein 1967). But the number of follicles, opening diameter, and the volume of

the follicle are the most important factors for the permeability (Otberg et al. 2004).

Most of the actives enter through the intracellular micro-route mechanism, so it is

required to enhance the permeation or disrupt the architecture of the surface layer

(Barry 2001). Parameters such as diffusibility, structure, geometry of the skin, and

the microcirculatory system are responsible for the penetration (Scheuplein 1967).

However, the actives or payloads should be ionic or polar in nature if the diffusion is

carried out by follicles. The diffusion mechanism can be well explained by Fick’s

first law. The concentration gradient is one of the major driving forces for the

absorption of the drug. The concentration is high at the outer membrane, while

deeper layers have low concentration. The chemical structure and the charge on the

molecule are also important for the percutaneous absorption. Electrolytes and ions

have a slow rate of absorption. The major challenging task for polar compounds is

the low partitioning into the stratum corneum. This problem can be minimized by

increasing the lipophilicity or by increasing the chain length of the compounds.

Interestingly, it is also to be noted that too much lipophilic drug can tend to form a

reservoir in the stratum corneum (Wiechers 1989). Other challenges such as disease,

age, skin first-pass metabolism, reservoir capacity of the skin, irritation, and toxicity

can also decrease the penetration of the drug (Katare et al. 2010).

The critical requirements for the dermal delivery of therapeutic agents are as

follows: (1) should have low volume and molecular weight, (2) should possess good

solubility in lipoidal and aqueous phase, (3) should have high diffusivity rate in the

outermost layer of the skin (stratum corneum), and (4) should have less accumula-

tion in the stratum corneum (Wiechers 1989). Some realistic promises of delivering

the drug or payloads by the topical route are high surface area, low toxicity, no

stability-related problems (flocculation, creaming, sedimentation), protection from

enzymatic and hydrolytic degradation, reduction of water in transepidermal, and

have a high capacity to entrap the lipophilic drugs (Ghasemiyeh and Mohammadi-

Samani 2020). Several target locations of various skin diseases have been listed in

Table 14.1.

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Lipodermaceuticals: Technological Transformations

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