Intercellular space (Inter-keratinocyte gap)

The inter-keratinocyte gap refers to the microscopic intercellular space between keratinocytes in the various layers of the epidermis, including the stratum corneum and viable epidermis. This space is primarily filled with a specialized extracellular matrix composed of lipids (such as ceramides, cholesterol, and fatty acids) and structural components like hyaluronan, which are essential for maintaining the skin's permeability barrier. In the context of pharmacology and dermatology, the inter-keratinocyte gap is recognized as the major paracellular route for the delivery of topically applied drugs. Therapeutic strategies, particularly those involving advanced nanocarriers like lipid nanoparticles, aim to "enlarge" or widen these gaps temporarily to enhance the penetration of large or hydrophilic molecules that would otherwise be blocked by the intact skin barrier. While it is a critical site of action for penetration enhancers, the inter-keratinocyte gap is a histological and structural feature of the skin rather than a distinct molecular target, such as a receptor or enzyme. Pathological widening of this space, a condition known as spongiosis, is a hallmark of inflammatory skin disorders like atopic dermatitis.

Other names

Inter-keratinocyte gapIntercellular space of the epidermisParacellular pathway of the skinInter-keratinocyte spaceEpidermal intercellular space

Enhancement of drug flux by enlarging the inter-keratinocyte gap through the disruption of the stratum corneum lipid matrix and the induction of an occlusion effect that increases skin hydration.