Formulation and ex vivo characterization of a kaempferol transethosomal hydrogel for the prevention of UV-induced cutaneous damage

In this study, lipid nanovesicular systems such as ethosomes and transethosomes dispersions were studied as potential vehicles for the cutaneous administration of kaempferol, a flavonol with antioxidant and chemopreventive properties. The lipophilicity of kaempferol requires specialized delivery systems suitable for transdermal administration. Kaempferol loading in ethosomes and transethosomes, prepared by ethanol injection methods, was investigated. The morphology of the vesicles was studied by cryogenic electron microscopy and by small angle X-ray scattering, while the size distribution was assessed by photon correlation spectroscopy. To make transethosome dispersions suitable for cutaneous application, Pluronic F-127 was used as a gelling agent. The physicochemical stability of the formulations was evaluated over a period of 3 months. To study the effect of the applied formulations on the skin, spreadability and leakage tests were performed. In vitro permeation studies were conducted using Franz diffusion cells and HPLC, to evaluate the diffusion kinetics of Kaempferol from the formulations. The evaluation of the dispersion macroscopic stability enabled to select transethosomes, loaded with 0.25 mg/ml of kaempferol. The results showed a promising 96% entrapment capacity, corresponding to 0.24 mg/ml and physicochemical stability of transethosomes, both in terms of size distribution and kaempferol content. Quantitative analysis via HPLC revealed that the drug diffuses more slowly from Pluronic-containing lipid formulations. Conversely, enhanced permeation through the membrane was observed for transethosomes. The ex vivo study on human skin explants demonstrated that the kaempferol-loaded transethosomal gel is able to limit the oxidative damage induced by UV exposure.