alexa Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement.
Dermatology

Dermatology

Hair Therapy & Transplantation

Author(s): Williams AC, Barry BW

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Abstract A series of terpenes has been assessed as skin penetration enhancers towards the model polar penetrant 5-fluorouracil (5-FU). Cyclic terpenes were selected from the chemical classes of hydrocarbons (e.g., alpha-pinene), alcohols (e.g., alpha-terpineol), ketones (e.g., carvone), and oxides (e.g., 1.8-cineole, ascaridole). Permeation experiments were performed on excised human epidermal membranes and the terpenes varied in their activities; alpha-pinene only doubled the permeability coefficient of aqueous 5-FU, whereas 1.8-cineole caused a near 95-fold increase. Essential oils, e.g., chenopodium (70\% ascaridole), were less effective than the corresponding isolated terpenes, 5-FU is less soluble in the terpenes than in water, and the terpenes did not exert their action by increasing partitioning of the drug into the membranes as illustrated by stratum corneum:water partitioning studies. The penetration enhancers increased drug diffusivity through the membranes, an effect which correlated empirically with the enhancer activities. The principal mode of action of these accelerants may be described by the lipid-protein-partitioning theory: the terpenes interacted with intercellular stratum corneum lipids to increase diffusivity, and the accelerant effects were not due to partitioning phenomena. Keratin interaction was assumed negligible.
This article was published in Pharm Res and referenced in Hair Therapy & Transplantation

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