Chemical Penetration Enhancers: Classification and Mode of Action

  • Nina Dragicevic
  • Jelena Predic Atkinson
  • Howard I. Maibach

Abstract

Chemical penetration enhancers have been studied for a long time as a means to increase the transport of a drug across the skin barrier. They exert their effect by using a range of mechanisms such as disrupting the lipid bilayer structure in the stratum corneum (SC) and thereby increasing the drug’s diffusion coefficient, extracting lipids from the SC, altering the solvent nature of the SC and consequently modifying the drug partitioning coefficient, acting on intracellular keratin, etc. Chemical enhancers can be categorised into different groups on the basis of their chemical structure. Solvents like alcohols and polyols mainly increase drug’s solubility in the SC and improve partitioning of the drug into the SC. Furthermore, some solvents (dimethyl sulphoxide (DMSO), ethanol) may extract lipids, making the SC more permeable as they form aqueous channels. Laurocapram (Azone®) and oleic acid are examples of chemical enhancers that can insert themselves into the SC lipid bilayer structures and disrupt the packing of the lipids. The result of this is that the lipid structure of the SC becomes more fluid and the diffusion coefficient of the permeant is increased. Ionic surfactants and DMSO also interact with the keratin structure in the corneocytes. This opens up the tight protein structure and leads to an increased diffusion coefficient through the corneocytes, being however not of great importance as the intercellular route, and not the intracellular route, is the major penetration pathway through the SC. Despite being very effective in enhancing drug permeation through the skin, many chemical penetration enhancers have a limited use in topical and transdermal drug delivery systems because they can cause skin irritation.

Keywords

Chemical penetration enhancer Skin Stratum corneum Mode of action Terpenes Ethanol Lipid bilayer 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Nina Dragicevic
    • 1
  • Jelena Predic Atkinson
    • 2
  • Howard I. Maibach
    • 3
  1. 1.Department of ProductionApoteka “Beograd” (Pharmacy “Belgrade”)BelgradeSerbia
  2. 2.LondonUK
  3. 3.Dermatology ClinicUniversity of California San FranciscoSan FranciscoUSA

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