Abstract
Flavonoids are plants pigments. Flavonoids can be observed by the naked eye as they form the amazing colors of flower petals. Flavonoids are classified on the basis of their chemical structure composed of two aromatic cycles connected by three carbons: C6-C3-C6, chains are closed in hexa- or pentagonal oxygenated heterocyclic ring. Flavonoids present interesting physiological activates that permit their usefulness as medicaments, especially for their free radical scavenging ability. Indeed, flavonoids activates were the object of numerous review articles.Among flavonoids, quercetin is the molecule the most distributed in nature that presents the strongest antioxidant and antiinflammatory activities in comparison to other molecules of this family. In general flavonoids and specially quercetin present poor water solubility, thus limiting their absorption/penetration and as a result their efficiency.Starting for the idea that the skin is the largest organ of the human body and the organ, which the most exposed to oxidative stress due to UV irradiation or other corrosive and irritating chemicals. Quercetin is a candidate for skin supplementation with exogenous antioxidant. The first objective of the thesis is to develop several formulations at the nanometric range for quercetin, in order to increase its water solubility and to enhance its physicochemical properties. The second objective is to compare these formulations in terms of quercetin loading capacity, cellular toxicity of quercetin and its formulations on HaCaT cells (keratinocytes), THP-1 cells (monocytes) and Vero cells (epithelial). Then, the protective activity of quercetin in vitro on cells to finally put in evidence the increase of quercetin in vivo skin penetration in formulations.In this project, three nanoformulations approaches (smartCrystals®, lipid nanocapsules and liposomes) were tested for the increase of quercetin water solubility. The formulations were optimized for scale up to industrial scale at the level of preparation method, also in the excipients compositions for higher affinity to quercetin. The formulations were characterized in terms of particle size, PDI, quercetin loading, crystallinity evaluation and quercetin in vitro release profile. Then, formulations were compared in interaction with HaCaT and THP-1 cells for their cellular toxicity and protective activity. Finally, two formulations (quercetin smartCrystals® with TPGS and quercetin lipid nanocapsules 20) were selected and compared for the enhancement of the in vivo skin penetration of quercetin.This project propose a solution for the successful formulation of quercetin enabling its efficient skin delivery. This project can be extrapolated to industrial level for quercetin and other poorly water soluble molecules that present limited efficiency due to their low skin penetration capacity.