Plant foods contain many bioactive compounds in addition to those which are traditionally considered as nutrients, such as phytochemicals. Among these, polyphenols like resveratrol, curcumin, quercetin, catechin represent one of the most attractive family of naturally bioactive molecules since many studies report their beneficial effects due to anti-oxidant, anti-microbial and anti-proliferative activities. Although these substances hold promises for supporting more conventional therapies, major drawbacks are represented by their low solubility, stability ad bioavailability. In the last years, nanotechnology has received considerable attention to enhance delivery of phytochemicals. Bioactive molecules can be loaded into biocompatible and biodegradable nanoparticles, which can enhance their absorption and bioavailability, protect them from degradation, enhance their stability, prolong circulation time, exhibit differential uptake efficiency in cancer cells and lower toxicity. Nanoemulsions are colloidal dispersions in which main components are oil, emulsifying agents, and aqueous phases. A variety of plant-derived essential oils can be used to prepare nanoemulsions and lipophilic phytochemicals can be incorporated in the hydrophobic core.
We have recently prepared and characterized functional oil-in-water (O/W) nanoemulsions (NE) with an average size of 100 nm , able to load and delivery resveratrol, a polyphenol with well known pleiotropic effects, in cancer cell lines of different origin. Our data, showing a strong reduction of the cell population after cell treatment with resveratrol-loaded NE (NE-RV), set the basis for investigating, in this research project, the mechanisms underlying the antiproliferative effects exerted by NE-RV and compare them to those activated by free resveratrol.
Many hydrophobic bioactive agents are currently unable to fully exhibit their potential health benefits because they have either low or variable bioavailability. Different types of bioactive molecule have different requirements to increase their bioavailability due to the unique set of factors that limit their delivery, absorption, or transformation. Nanoemulsions (NEs) are proposed for numerous applications in pharmacy as drug delivery systems because of their capacity to solubilize non-polar active compounds. However, in recent years, the use of nanotechnology to enhance delivery of phytochemicals to tumors or cancer cells for improving therapeutic efficiency has received considerable attention. Significant progress has been made in nanoemulsion design, production, and testing but more studies are required to optimize nanoemulsion compositions for enhancing their anti-cancer activity and lowering their toxicity, side-effects, and cost. In particular during the past decade, several NEs have been approved under clinical investigation, such as Estrasorb and Flexogan for topical applications, or Cationorm and Restasis as ophthalmic emulsions.
However, nowadays NEs are employed for many other applications, such as parenteral and transdermal delivery of lipophilic drugs, as well as for oral and sublingual delivery. In addition, NEs show muco-adhesive properties, enhancing the permeability of the mucous layer for an intranasal administration. NEs are composed by oil droplets (potential reservoir for hydrophobic drugs) dispersed in an aqueous phase and surfactants, such as Tween 20, 80 etc. These surfactants are useful to obtain stable NEs since they are prone to phase separation. In particular, by using the appropriate amount of surfactant no apparent flocculation or coalescence are observed. Droplet size typically falls in the range of 20-200 nm in order to improve pharmacological effects and intracellular penetration in biological tissues, or enhance skin retention, in case of topical applications. Also the small size of the droplets in NEs enhances their stability, by decreasing gravitational separation and droplet aggregation. A mean droplet size ranging from 10-100 nm was obtained by modulating the oil/surfactant ratio. In particular, droplet size decreases with increasing in surfactant concentration and time of sonication. The possibility to modulate the dimensions is particularly useful to obtain the suitable vectors for a specific application. Another advantage of NE consists in using natural oils characterized by an intrinsic pharmacological effect, able to increase the delivered natural compound activities (anti-inflammatory, antioxidant, antibacterial, antiviral, anticancer and/or tissue regenerative activity).