Evaluation of sesquiterpenes as permeation enhancers for a model macromolecule across human skin in vitro

Abstract The objective of this study was to assess the in vitro transdermal permeation of a model macromolecular compound namely; fluorescein isothiocyanate - dextran 4 kDa (FD-4) across full thickness human skin by means of chemical enhancers. For this purpose, two sesquiterpenes derived from farnesol were synthesized and further evaluated. Transport studies were conducted using vertical Franz diffusion cells followed by tape stripping in an attempt to examine the disposition of FD-4 on and within the skin. The transport of FD-4 across skin was significantly enhanced in the presence of farnesol and two of its derivatives: A 3.02, 2.67 and 3.74-fold increase was observed compared to a control formulation free of sesquiterpenes. Light microscopy studies showed detachment of the superficial layers and in some cases loosening and swelling of cell layers. Differential scanning calorimetry (DSC) studies of stratum corneum (SC) sheets treated with the sesquiteprenes indicated that enhanced permeation of FD-4 was mainly achieved by disruption and fluidization of the SC lipid bilayers whereas infrared spectroscopy (AT-FTIR) data indicated significant decreases in peak intensity. The results showed that the co-administration of selected sesquiterpenes with FD-4 increased its transport across the skin and might be advantageous for transdermal delivery of macromolecules.