Transdermal penetration enhancing effect of the N-alkylamide spilanthol

Abstract

The dermal penetration of compounds may be influenced by other compounds when mixtures are presented to the skin. Plant extracts, often used in cosmeceuticals, are complex mixtures of wanted bio-actives as well as undesirable impurities like nanoparticles and mycotoxines. A major question is if plant bio-actives (like spilanthol) can significantly alter the dermal penetration of other compounds which can be actives (like testosterone) or impurities (like mycotoxins). If so, the qualification assessment of the product quality needs to include this influence within the Quality-by-Design strategy. Therefore, the concentration-dependent penetration promoting effect of spilanthol was investigated on the three CART transdermal model compounds i.e. caffeine, ibuprofen and testosterone [1]. It was shown that spilanthol has a compound and concentration dependent penetration enhancing effect. No significant penetration enhancing effect for ibuprofen has been observed. However, with increasing spilanthol concentration (from 0 up to 1%, m/V), the permeability of caffeine increases, resulting in an enhancing ratio (ER) of 4.60 ± 0.49 (mean ± SEM, n=4). For testosterone, a maximal penetration enhancing concentration of 0.5% spilanthol was found (ER = 4.13 ± 0.44 (mean ± SEM, n=3)). Our findings with these model compounds are also confirmed with mycotoxins [2]. In conclusion, the existence of a significant mutual influence of compounds towards skin penetration should always be considered as part of the functional quality evaluation or in topical product development. References [1] B. Baert, E. Deconinck, M. Van Gele, M. Slodicka, P. Stoppie, S. Bode, G. Slegers, Y. Vander Heyden, J. Lambert, J. Beetens, B. De Spiegeleer. Transdermal penetration behaviour of drugs: CART-clustering, QSPR and selection of model compounds, 2007, Bioorganic & medicinal chemistry, 15(22): 6943-6955. [2] B. De Spiegeleer, J. Boonen, L. Veryser, L. Taevernier, S.V. Malysheva, J. Diana Di Mavungu, S. De Saeger, N. Roche, P. Blondeel. Skin penetration enhancing properties of the plant N-alkylamide spilanthol, 2012, manuscript in preparation