In recent years, a great deal of attention has been paid to natural compounds due to their many biological effects. Polyphenols are a class of plant derivatives that have been widely investigated for preventing and treating many oxidative stress-related pathological conditions, such as neurodegenerative and cardiovascular diseases, cancer, diabetes mellitus and inflammation. Among these polyphenols, resveratrol (RSV) has attracted considerable interest owing to its high antioxidant and free radical scavenging activities. However, the poor water solubility and rapid metabolism of RSV lead to low bioavailability, thus limiting its clinical efficacy. After discussing the main biochemical mechanisms involved in RSV biological activities, this review will focus on the strategies attempted to improve RSV effectiveness, both for systemic and for topical administration. In particular, technological approaches involving RSV incorporation into different delivery systems such as liposomes, polymeric and lipid nanoparticles, microemulsions and cyclodextrins will be illustrated, highlighting their potential clinical applications. In addition, chemical modifications of this antioxidant aimed at improving its physicochemical properties will be described along with the results of in vitro and in vivo studies.

Idebenone (IDE), a strong antioxidant widely investigated for the treatment of neurodegenerative diseases and skin disorders, shows low oral and topical bioavailability due to its unfavorable physico-chemical properties. In this work, to improve IDE topical effectiveness, we explored a two-steps approach: (1) we synthesized an IDE ester (IDEPCA) with pyroglutamic acid, a molecule whose hydrating effects are well known; (2) we loaded IDEPCA into solid lipid nanocarriers (SLN). We evaluated in vitro antioxidant and anti-glycation activity and in vivo hydrating effects after topical application in human volunteers from gel vehicles of IDEPCA SLN in comparison to IDE SLN. All SLN showed good technological properties (mean particle size < 25 nm, polydispersity index < 0.300, good stability). The oxygen radical absorbance capacity assay showed that IDEPCA SLN and IDE SLN had similar antioxidant activity while IDEPCA SLN were more effective in the in vitro NO scavenging assay. Both IDEPCA and IDE SLN showed the same effectiveness in inhibiting the formation of advanced glycation end products. In vivo experiments pointed out a better hydrating effect of IDEPCA SLN in comparison to IDE SLN. These results suggest that the investigated approach could be a promising strategy to obtain topical formulations with increased hydrating effects.

Idebenone (IDE) is a strong antioxidant that has been proposed for the treatment of skin disorders, including skin ageing. Unfavorable physico-chemical properties make IDE a poor skin permeant where effectiveness could be improved by its loading into suitable delivery systems such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). In this work, we designed novel IDE-loaded NLC containing tocopheryl acetate (VitE) as a liquid component to obtain a synergic effect between IDE and VitE. The resulting NLC showed small particle sizes (24–42 nm), low polydispersity indices (<0.300), good stability, and were assessed for their in vitro antioxidant activity and in vivo topical effects. IDE-loaded SLN and NLC showed a high antioxidant activity in in vitro assays (DPPH and reducing power method) and provided a similar and significant protection from oxidative stress of fibroblast cells, HS-68, exposed to UV light. After a two-week topical treatment of human volunteers with gels containing IDE-loaded SLN or NLC, a similar increase in skin hydration was observed, while IDE NLC reduced skin pigmentation to a greater extent than IDE SLN. These results suggest that co-loading IDE and VitE into NLC could be a promising strategy to obtain topical formulations with improved photo-protection.

Some vegetable oils have many biological properties, including UV-absorbing capacity. Therefore, their use has been suggested to reduce the content of organic UV-filters in sunscreen products. In this work, we investigated the feasibility of developing oil-based vehicles with a high sun protection factor (SPF) using pomegranate oil (PMG) and shea oil (BPO) in association with different percentages of organic UV-filters (octyl– methoxycinnamate, butyl methoxydibenzoylmethane, and bemotrizinol). We characterized the spreadability, occlusion factor, pH, and required hydrophilic lipophilic balance of the resulting formulations, and did not observe relevant differences due to the incorporation of vegetable oils. The in vitro spectrophotometric determinations of SPF values highlighted that the addition of BPO (1% (w/w)) and PMG (1% (w/w)) resulted in an increase in SPF in comparison with the same formulations that contained only organic UV-filters. The SPF increase was more significant for the formulations that contained lower amounts of organic UV-filters. The results of this study supported the hypothesis that including suitable vegetable oils in sunscreen formulations could be a promising strategy to design products with a lower content of organic UV-filters.

Lipid nanoparticles (LNPs) have been proposed as carriers for drug skin delivery and targeting. As LNPs effectiveness could be increased by the addition of chemical penetration enhancers (PE), in this work, the feasibility of incorporating PE into LNPs to improve idebenone (IDE) targeting to the skin was investigated. LNPs loading IDE 0.7% w/w were prepared using hydrophilic (propylene glycol, PG, 10% w/w or N-methylpyrrolidone, NMP, 10% w/w) and/or lipophilic PE (oleic acid, OA, 1% w/w; isopropyl myristate, IPM, 3.5% w/w; a mixture of 0.5% w/w OA and 2.5% w/w IPM). All LNPs showed small sizes (<60 nm), low polydispersity index and good stability. According to the obtained results, IDE release from LNPs was not the rate-limiting step in IDE skin penetration. No IDE permeation was observed through excised pigskin from all LNPs, while the greatest increase of IDE penetration into the different skin layers was obtained using the mixture OA/IPM. The antioxidant activity of IDE-loaded LNPs, determined by the oxygen radical absorbance capacity assay, was greater than that of free IDE. These results suggest that the use of suitable PE as LNPs components could be regarded as a promising strategy to improve drug targeting to the skin.