Percutaneous Permeation Enhancement by Terpenes: Mechanistic View

Abstract

Abstract. A popular approach for improving transdermal drug delivery involves the use of penetration enhancers (sorption promoters or accelerants) which penetrate into skin to reversibly reduce the barrier resistance. The potential mechanisms of action of penetration enhancers include disruption of intercellular lipid and/or keratin domains and tight junctions. This results in enhanced drug partitioning into tissue, altered thermodynamic activity/solubility of drug etc. Synthetic chemicals (solvents, azones, pyrrolidones, surfactants etc.) generally used for this purpose are rapidly losing their value in transdermal patches due to reports of their absorption into the systemic circulation and subsequent possible toxic effect upon long term application. Terpenes are included in the list of Generally Recognized As Safe (GRAS) substances and have low irritancy potential. Their mechanism of percutaneous permeation enhancement involves increasing the solubility of drugs in skin lipids, disruption of lipid/protein organization and/or extraction of skin micro constituents that are responsible for maintenance of barrier status. Hence, they appear to offer great promise for use in transdermal formulations. This article is aimed at reviewing the mechanisms responsible for percutaneous permeation enhancement activity of terpenes, which shall foster their rational use in transdermal formulations.

Essential oil-mediated glycerosomes increase transdermal paeoniflorin delivery: optimization, characterization, and evaluation in vitro and in vivo

“…45 The present results have shown that STO contains mainly sesquiterpenes, which may improve the permeation of drugs by disrupting the lipid packaging of stratum corneum and/or disturbing the stacking of bilayers, and then enhance the penetration of glycerosomes into the skin, just as the function of terpenes in the invasomes. [46][47][48][49] Moreover, the permeation-enhancing effect of caryophyllene and aromadendrene identified in STO has been reported by recent research.…”

The application of anethole, menthone, and eugenol in transdermal penetration of valsartan: Enhancement and mechanistic investigation

“…The log P value of terpenes (Table 1) appears as a predictor in many QSAR models (Yamashita and Hashida 2003;Geinoz et al 2004;Sapra et al 2008). Kang et al (2007) determined permeability coefficient of different terpenes experimentally using human skin and employed non-linear regression model.…”

“…Further, quite a few terpenes are included in the list of Generally Recognized As Safe (GRAS) agents issued by the US Food and Drug Administration (US FDA) (Aqil et al 2007;Sapra et al 2008). They cause no skin toxicity or if any, only mild irritation.…”

Vitex Agnus-Castus L. Essential Oil Increases Human Erythrocyte Membrane Fluidity

“…Similar results were obtained for limonene and other related compounds (30). The ability to increase the susceptibility of the membrane to the penetration of various compounds seems to be a general characteristic of cyclic terpens (31). To date, several constituents of Vac essen tial oil -1,8-cineole, a-pinene, limonene (31), have been used for increasing percutaneous permeation and to facilitate the passage of drugs through cellular membranes (32).…”