Layers of Skin involved in drug transport
1. Stratum Corneum:
Outermost layer of the skin.
Composed mainly of dead skin cells filled with keratin (keratinocytes).
Acts as the primary barrier to drug permeation due to its tightly packed cells and lipids.
If a drug can pass through this layer, it's likely to continue its journey through the deeper layers of the skin.
2. Epidermis (excluding Stratum Corneum):
Immediately below the stratum corneum.
Consists of living cells and does not have blood vessels.
The drug continues its passive diffusion through this layer after crossing the stratum corneum.
3. Dermis:
Located below the epidermis.
Rich in blood vessels and lymph vessels.
Once the drug reaches this layer, it can be absorbed into the systemic circulation.
For a drug to be effectively delivered via a TDDS, it must be able to penetrate through all these layers, with the stratum corneum being the most challenging barrier. Factors like the drug's molecular size, lipophilicity, and the use of permeation enhancers can impact its ability to traverse these layers
Routes of Skin Penetration
The skin, being a multifaceted organ, offers several routes for drug penetration:
1. Transcellular Route:
In this route, the drug molecule passes directly through the cells of the stratum corneum and subsequently the underlying epidermal cells.
It involves the molecule moving in and out of the cells and intercellular lipid domains.
This route can be challenging due to the hydrophobic nature of the cell membranes and the lipophilic surroundings.
2. Intercellular Route:
Here, the drug molecule bypasses the cells and moves through the lipid-rich domains present between the cells of the stratum corneum.
Given that these regions are lipophilic, lipophilic drugs often find this route more permeable. However, the tortuous path can hinder drug movement.
3. Transappendageal (or Shunt) Route:
This route involves drug movement through skin appendages like hair follicles, sweat glands, and sebaceous glands.
While these structures occupy a minimal area of the skin, they can be essential for the penetration of certain drugs, especially macromolecules or for iontophoretic delivery.
4. Subcutaneous Route:
Though not typically utilized in TDDS, this route involves drug delivery into the subcutaneous tissue layers, usually via injections. It bypasses the barrier properties of the skin altogether.
