Liposomes for the co-delivery of naturally occurring polyphenols (quercetin and resveratrol): characterization and in vitro/in vivo evaluation

Polyphenolic compounds, such as quercetin and resveratrol, have gained great interest in the pharmaceutical research area due to their beneficial properties, namely antioxidant, antiradical, antiinflammatory, anticarcinogenic, antibacterial, and antiviral effects [1-2]. This wide spectrum of therapeutic activities, coupled with their safety profile and natural origin (they are commonly found in fruits and vegetables), make quercetin and resveratrol very attractive candidates for the development of novel pharmaceutical products [3]. However, the use of these two polyphenols is limited by their poor water solubility and instability, which lead to subtherapeutic levels and require higher doses to be administered, thus hampering their beneficial properties and potential health benefits [4,5]. In this framework, nanoparticulate delivery systems have been proven to be effective in protecting, controlling the release, and enhancing the action of different bioactive compounds. The current study was carried out to determine whether the combination of the two polyphenols delivered by liposomes would increase their bioactivity in coping with oxidative stress and inflammation implicated in pre-cancerous/cancerous skin conditions. The formulation is also expected to have superior efficacy as compared to the free agents, owing to the advantages offered by the nanovector, specifically tailored for skin delivery. Quercetin and resveratrol co-incorporated in biocompatible liposomes were characterized in terms of physico-chemical and antioxidant properties. Their morphology and lamellar assembly were also probed. The in vitro cytotoxicity/cytocompatibility and uptake of the two polyphenols were tested in human fibroblasts, as well as their activity against free radicals (ROS). Further, the efficacy and safety of the co-formulated polyphenols were assessed in vivo by testing their activity against chemically- induced oedema and leukocyte infiltration. Therefore, the proposed approach based on polyphenol vesicular formulations may be of value in the treatment of pre-cancerous/cancerous skin conditions associated with inflammation and oxidative stress.