Summary:
The aim of the present study is the formulation and optimization of topical resveratrol microemulsions, and the assessment of In Vitro transdermal permeation and In Vivo preventive and therapeutic efficacy in UV induced skin inflammation.
UV radiation promotes Reactive Oxygen Species formation in dermis and epidermis, causing direct and indirect damage linked to inflammation. Resveratrol is a naturally occurring polyphenol with well-studied antioxidant and anti-inflammatory action. Resveratrol’s sensitivity to sunlight oxidation and extensive per os first pass metabolism have hindered its wide use. Microemulsions are spontaneously forming thermodynamically stable colloidal formulations able to increase resveratrol’s solubility and stability, as well as transdermal bioavailability.
Formulating for Efficacy® was used for the selection of optimal oily phase excipients. Design of Experiments was used for microemulsion optimization. With an oily phase consisting of Transcutol®: Labrasol (24:76), and an overall formulation of Oil: Surfactant System: Water (26: 7: 67), optimal microemulsion contained 1,9% resveratrol. It exhibited maximum cumulative permeation and maximum permeated dose as a percentage of applied dose, when compared to formulations with higher resveratrol concentration. This behavior was attributed to microemulsion’s type, Winsor Ι, which was spontaneously converted to Winsor III when temperature raised over 25oC. It showed acceptable physicochemical stability over two months. Preliminary In Vitro permeation study showed that StratM® membrane was a successful tool for microemulsion optimization.
A comparative In Vitro permeation study was performed, using optimal microemulsion 1.9% and an optimal resveratrol gel 5% and cream 6%, from earlier resveratrol formulation optimization studies. For the In Vitro study, vertical Franz cells and StratM® artificial membrane as well as human stratum corneum were used. StratM® membrane exhibited inadequate resistance to microemulsions resulting to a thousand times overestimation of cumulative permeation. Human stratum corneum retention study showed an 2.5fold increase in resveratrol retention for the microemulsion 1.9% compared to resveratrol cream 6% or gel 5%. This increased retention was attributed to the combination of Winsor type change and the use of chemical permeation enhancer Transcutol®, which has been reported to increase resveratrol retention in human stratum corneum.
In Vivo anti-inflammatory action of the compared formulations was performed on hairless mice type SKH-1. Inflammatory response was induced by UV radiation and was monitored through TEWL, hydration, redness, skin thickness, melanin sebum and pH measurements. Antera Miravex® was used to assess hemoglobin and skin roughness levels. Photographical documentation and histopathological observation were used to confirm In Vivo findings, as resveratrol microemulsion 1.9% successfully hindered inflammatory culmination and enabled faster health reassurance. In Vivo In Vitro correlation performed confirmed in vivo findings and the predictive value of In vitro transdermal permeation studies in predicting In Vivo anti-inflammatory efficacy.
Keywords:
Resveratrol, Microemulsion, Percutaneous Penetration, Anti-inflammatory, UV induced Skin Inflammation, Mice
