Drugs can be absorbed through the skin, a process known as transdermal or percutaneous absorption. This involves an active substance passing across the skin layers to reach the bloodstream for systemic circulation. This route is used in modern medicine to deliver controlled doses of medication over time. However, this pathway is also a significant route for accidental exposure to toxic substances in occupational and domestic settings. Understanding transdermal absorption is important because the skin acts both as a protective barrier and a controlled delivery system.
How the Skin Acts as a Barrier
The skin functions primarily as a defense against the external environment, mainly due to its outermost layer, the epidermis. The most significant barrier to absorption is the stratum corneum, which is structured like “brick and mortar.”
The “bricks” are corneocytes (flattened, dead skin cells rich in keratin), and the “mortar” is a surrounding lipid matrix. This lipid-rich matrix is highly hydrophobic, repelling water-soluble substances and preventing most molecules from passing through.
The stratum corneum is the rate-limiting step for transdermal drug delivery, dictating how quickly a substance enters the body. Once crossed, the substance enters the deeper, more permeable layers of the epidermis and the dermis. The dermis contains a dense network of blood vessels, allowing the absorbed substance to quickly enter the systemic circulation.
Chemical and Environmental Factors That Increase Absorption
A substance’s ability to penetrate the skin is highly dependent on its specific physicochemical properties. The molecular weight is a major factor, as molecules generally need to be relatively small, ideally less than 500 Daltons, to pass effectively through the dense stratum corneum. The substance must also possess a balance of lipid and water solubility to navigate the different skin layers. Fat-soluble, or lipophilic, compounds dissolve better in the lipid matrix of the stratum corneum, which is the main entry route.
Environmental conditions can significantly alter the skin’s barrier function and increase absorption. Skin hydration, often caused by applying an occlusive dressing, causes tissue swelling and softens the intercellular lipid pathways, which increases permeability. Raising the skin temperature enhances absorption by increasing blood flow to the dermal layer. Furthermore, chemical penetration enhancers in a formulation can temporarily disrupt the lipid barrier, making diffusion easier.
Intentional Drug Delivery Versus Accidental Exposure
Transdermal absorption is intentionally utilized in medicine through Transdermal Delivery Systems (TDS), most commonly patches, to achieve a steady, controlled release of medication. This method offers a significant advantage by bypassing the digestive system and the liver’s initial metabolism. This helps maintain a consistent drug concentration in the bloodstream.
Examples of medications delivered this way include nicotine for smoking cessation, hormone replacement therapy, and certain pain medications like fentanyl. The patch design ensures a sustained therapeutic effect, often lasting for days, which improves patient adherence.
In contrast, accidental exposure occurs when individuals come into contact with highly potent or concentrated substances. The danger of toxic exposure is that the skin acts as a silent entry point, without the immediate pain or sensation that accompanies an injection or ingestion.
Highly potent pharmaceuticals, such as fentanyl patches, pose a severe risk if misused, improperly disposed of, or accidentally transferred to a child. Even contact with industrial solvents, concentrated pesticides, or certain cleaning agents can lead to systemic poisoning. These chemicals are often highly lipid-soluble, maximizing their ability to penetrate the skin barrier. Accidental exposure, particularly in children, has been associated with severe or fatal outcomes due to the high drug load contained within transdermal patches.