Acmella oleracea and Zingiber officinale (ginger) are two plants of great interest due to their antioxidant, antimicrobial, and especially anti-inflammatory properties. These effects are mainly attributed to the presence of bioactive compounds such as spilanthol in Acmella oleracea and [6]-gingerol in Zingiber officinale. However, [6]-gingerol is primarily metabolized at the gastrointestinal and hepatic levels after oral administration, limiting its systemic bioavailability and effectiveness. In this study, a cream formulation containing both extracts was prepared using a preformed commercial transdermal vehicle and characterised through rheological studies. The ex vivo skin permeation of spilanthol and [6]-gingerol was evaluated using Franz diffusion cells. Results showed that the presence of Acmella oleracea lipophilic extract promoted the permeation of [6]-gingerol. Moreover, no histological alterations were observed in explanted human skin after transdermal application in a fluidic dynamic system. Based on these findings, topical administration of a formulation containing both Zingiber officinale and Acmella oleracea lipophilic extracts appears to be a promising strategy for enhancing the skin permeability of the active ingredients and, specifically for [6]-gingerol, avoiding its transformation in the gastrointestinal tract.
