Abstract
A preformulative study was conducted to produce and characterize ethosomes for the transdermal delivery of gossypin. This plant-derived compound possesses many pharmacological properties, including antitumoral potential. Ethosome dispersions were designed as transdermal delivery systems for gossypin, employing two different production procedures. The evaluation of vesicle size distribution by photon correlation spectroscopy, morphology by cryogenic transmission electron microscopy, and gossypin entrapment capacity, as well as in vitro release and permeation by vertical diffusion cells, enabled us to select a production strategy based on the injection of a phosphatidylcholine ethanolic solution in water. Indeed, vesicles prepared by this method were almost unilamellar and measured roughly 150 nm mean diameter while displaying an entrapment capacity higher than 94%. Moreover, vesicles prepared by the ethanol injection method enabled us to control gossypin release and to improve its permeation with respect to the solution of the drug. To obtain semi-solid forms suitable for cutaneous gossypin administration, ethosome dispersions were thickened with 0.5% w/w xanthan gum, selected by a spreadability test. These ethosome gels were then further characterized by small- and wide-angle X-ray scattering, while their antioxidant activity was demonstrated in vitro by a radical scavenging assay. Finally, in vitro biological studies were conducted on A375 melanoma cell lines. Namely, wound healing and cell migration assays confirmed the potential antitumoral effect of gossypin, especially when loaded in the selected ethosomal gel. The promising results suggest further investigation of the potential of gossypin-loaded ethosomal gel in the treatment of melanoma.