Transferosomes and ethosomes for the trans-resveratrol permeation through the skin: a comparative study.

Introduction: The trans-resveratrol (t-res) is a non flavonoid polyphenol with promising properties for the treatment or prevention of different diseases. In particular, topical application of resveratrol could be advantageous in the prevention of skin cancer or in the treatment of inflammation-based diseases such as psoriasis. However, different studies demonstrated the importance of the formulation to enhance t-res delivery into or trough the skin. Nanocarriers, such as ethosomes and transferosomes, have been successfully used to deliver drugs with different characteristics into or through the skin. Purpose: The aim of the present work was to develop a nanocarrier-based formulations for skin delivery of t-res. Methods: Ethosomes or transferosomes containing t-res were prepared by a modified hand-shaking method followed by extrusion or sonication. All the formulations were characterised in terms of mean diameter, size distribution (I.P.), t-res loading, t-res stability upon encapsulation during storage at 4°C. The inhibition of reactive oxygen species (ROS) and lipids peroxidation in human keratinocyte (HaCaT) cell line stimulated with H2O2 for 24 h and then incubated with the t-res containing nanocarriers was investigated. Moreover, for all the formulations, ex vivo permeation studies on porcine skin was carried out by means of Franz diffusion cells. At appropriate intervals (0.5, 1, 2, 4, 6, 24 h), an aliquots of the receptor medium were withdrawn and the t-res concentration was determined by HPLC. Results: All the t-res containing carriers were characterised by a very high (between 70 to 100%) encapsulation efficiency, a limited t-res release at 4°C during the storage and stability of resveratrol in its trans form. Nanocarriers encapsulating t-res reduced, in a concentration-dependent manner, ROS production induced by H2O2, with the higher effect observed in the case of ethosomes. Permeation studies showed that only ethosomes were able to promote t-res permeation through porcine skin and this effect was affected by lipid composition of the carrier. Conclusions: In this work, transferosomes showed the highest encapsulation efficiency and the lowest t-res release. On the other hand, only ethosomes were able to promote t-res permeation through the skin.