Investigating the interactions of resveratrol with phospholipid vesicle bilayer and the skin: NMR studies and confocal imaging

In this work, phospholipid vesicle-based nanoformulations were developed to deliver antioxidant resveratrol (RSV) to the skin. Penetration enhancer-containing vesicles (PEVs) were prepared adding Oramix™ CG110 or Lauroglycol™ FCC to phosphatidylcholine to favor RSV diffusion through the skin, which was investigated using Franz cells. Vesicles were approximately 100 nm in size, negatively charged and fairly round in shape, as shown via transmission electron microscopy. Nuclear magnetic resonance studies were performed to investigate the RSV/vesicle interactions at the molecular scale, which revealed that RSV was deeply embedded in the bilayer, as shown by the restricted mobility of the drug. Moreover, PEVs improved drug local accumulation 1.7- to 2.1-fold, as compared to the control liposomes. Confocal imaging displayed broadened intercellular spaces in the viable epidermis of PEVs treated skin and high degree of hydration, which are presumably due to the occlusive film formed on the skin surface by the vesicles. These phenomena may be responsible for the higher RSV accumulation achieved when administering PEVs, as compared to control liposomes. Finally, the toxicity of the vesicular formulations was evaluated in vitro against 3T3 fibroblasts, showing no alteration on cell viability after 24 h incubation with RSV loaded vesicles. The results from this study suggest that the proposed formulations may be a potential therapeutic alternative to treat skin disorders associated with oxidative stress.