The strategic use of the skin’s accessory structures, specifically the hair follicles and eccrine sweat glands, as alternative conduits for the absorption of therapeutic compounds into the underlying viable skin and systemic circulation. While this route is generally considered a minor absorption pathway, it can become significant for certain molecules, particularly those that are highly polar or possess unfavorable characteristics for traversing the main stratum corneum barrier. It offers a valuable, alternative shunt route for systemic drug delivery.
Origin
This concept arose from detailed dermatological studies that observed drug penetration patterns deviating from the expected intercellular lipid matrix diffusion, particularly for small, hydrophilic molecules. The appendages, acting as relative shunts or bypass routes, were subsequently identified as important alternative routes of entry. Pharmaceutical formulation scientists now actively seek to utilize this pathway for molecules with otherwise poor overall transdermal penetration properties.
Mechanism
The drug molecules bypass the dense lipid lamellae of the primary stratum corneum by migrating down the follicular opening and into the sebaceous gland or eccrine sweat gland ducts. Since the epithelial lining of these appendages is significantly less keratinized and more permeable than the surrounding stratum corneum surface, it offers lower diffusional resistance. Strategic utilization of this pathway is a formulation-dependent approach to enhance the overall drug flux and systemic uptake.
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