Transdermal absorption is a process where substances applied to the skin surface move through its layers and enter the bloodstream. This method allows therapeutic agents to reach the systemic circulation, bypassing the digestive system and liver metabolism. Transdermal administration provides a consistent and sustained release of medication, offering an alternative to oral or injectable routes.
The Skin’s Protective Barrier
The skin, the body’s largest organ, acts as a primary protective barrier against the external environment. It consists of three main layers: the epidermis, dermis, and hypodermis. The outermost layer, the epidermis, is further divided into sub-layers, with the stratum corneum being the most superficial.
The stratum corneum is composed of multiple layers of flattened, dead skin cells called corneocytes, which are rich in keratin. These corneocytes are embedded in a lipid-rich extracellular matrix, forming a “bricks and mortar” structure that effectively limits the entry of most substances. This unique composition of dead cells and lipids is the main obstacle to transdermal absorption.
How Substances Cross the Skin
Substances primarily penetrate the skin through two main pathways within the stratum corneum. The transcellular (or intracellular) pathway involves molecules passing directly through the corneocytes, navigating both their lipid membranes and hydrophilic interiors. This route, while the shortest distance, presents resistance as substances must repeatedly cross different chemical environments.
Conversely, the paracellular (or intercellular) pathway involves substances moving between the corneocytes, through the continuous lipid matrix. This route is more tortuous but is often the preferred path for many molecules. The choice of pathway depends largely on the substance’s properties, with lipid-soluble compounds favoring the intercellular route and water-soluble substances utilizing the transcellular route.
Minor routes for absorption also exist through skin appendages like hair follicles and sweat glands. These “shunt” pathways offer less resistance, particularly for smaller molecules. However, due to their limited surface area, around 0.1% of the total skin surface, their contribution to overall absorption is small for most substances.
Factors Affecting Absorption
Several factors influence the rate and extent to which substances are absorbed through the skin. The properties of the substance itself are important, including its molecular size and lipid solubility. Smaller molecules, ideally under 500 Daltons, and those with a balance of lipid and water solubility (a log partition coefficient between 1.0 and 4.0) penetrate the skin more effectively.
Skin properties also play a role in absorption. Skin hydration can increase permeability, as hydrated skin softens and swells, making it easier for substances to pass through. The thickness of the stratum corneum varies across different body sites, impacting absorption rates, with thinner areas like the face allowing for greater penetration than thicker areas like the palms or soles. Skin integrity, such as damaged or diseased skin, also influences absorption, leading to increased permeability. Additionally, the duration of contact, temperature, and occlusion (covering the application area with an impermeable dressing) can enhance absorption by increasing skin hydration and local blood flow.
Common Applications
Transdermal absorption is utilized in various medical and cosmetic applications. Transdermal patches are common examples, delivering medications like nicotine for smoking cessation, hormones for replacement therapy, and fentanyl for pain relief. These patches provide a controlled and continuous release of medication over an extended period, for several days.
Topical creams and gels are also used for transdermal delivery, ranging from localized treatments for skin conditions to formulations where some systemic absorption is desired, such as anti-inflammatory gels. The transdermal route is chosen for its convenience and to maintain steady drug levels in the bloodstream.