title: Skin penetration enhancing properties of the plant N-alkylamide spilanthol.
abstract: BACKGROUND
  Plants are often used for skin diseases in different ethnopharmacological systems. Local and systemic effects of topically applied compounds can be significantly increased by plant constituents having skin penetration enhancers.
  
  
  METHODS
  In this study, we examined the proposed penetration enhancing properties of spilanthol, an N-alkylamide abundantly present in several Asteraceae plants like Spilanthes acmella L., on three model drugs (caffeine, testosterone and ibuprofen). Moreover, as plants are frequently contaminated with toxic environmental substances, the mutual influence on the transdermal behavior between spilanthol and six model mycotoxins (aflatoxin B1, ochratoxin A, fumonisin B1, citrinin, zearalenone, T-2 toxin) was investigated.
  
  
  RESULTS
  Spilanthol exhibits component and concentration dependent penetration enhancing effects. No significant penetration enhancing effect for ibuprofen has been observed, but with increasing spilanthol concentration (from 0 up to 1w/V%), the permeability of caffeine increased, resulting in an enhancing ratio (ER) of 4.60. For testosterone, a maximal penetration enhancing concentration of 0.5% spilanthol was found (ER=4.13). Next to its beneficial applicability to increase local as well as systemic pharmacological effects of dermally co-administrated drug, this N-alkylamide negatively influences human health risk if spilanthol containing formulations are polluted with mycotoxins: the presence of spilanthol (0.3w/V%) induced a significant increase of permeability coefficient Kp of five investigated mycotoxins, with ER values ranging between 1.57 and 6.37. On the other hand, mycotoxins themselves do not significantly influence the transdermal behavior of spilanthol.
  
  
  CONCLUSIONS
  The existence of a significant mutual influence of compounds towards skin penetration should always be considered during the development or as part of the functional quality evaluation of topical products.
authors.affiliation: Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Bart.DeSpiegeleer@UGent.be
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
authors.forename: Jente
authors.initials: J
authors.lastname: Boonen
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Malysheva
authors.forename: José Diana Di
authors.initials: JD
authors.lastname: Mavungu
authors.forename: Sarah
authors.initials: S
authors.lastname: De Saeger
authors.forename: Nathalie
authors.initials: N
authors.lastname: Roche
authors.forename: Phillip
authors.initials: P
authors.lastname: Blondeel
authors.forename: Lien
authors.initials: L
authors.lastname: Taevernier
authors.forename: Lieselotte
authors.initials: L
authors.lastname: Veryser
mesh_terms: D016604:Aflatoxin B1 / Q000008:administration & dosage; D000577:Amides / Q000008:administration & dosage*; D002110:Caffeine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D066298:In Vitro Techniques; D008875:Middle Aged; D053284:Polyunsaturated Alkamides; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013605:T-2 Toxin / Q000008:administration & dosage; D013739:Testosterone / Q000008:administration & dosage
chemical_list: D000577:Amides; C489347:N-isobutyl-2E-decenamide; D053284:Polyunsaturated Alkamides; D002110:Caffeine; D013739:Testosterone; D016604:Aflatoxin B1; D013605:T-2 Toxin; D007052:Ibuprofen