# Formulation Strategies to Improve Oral Bioavailability of Ellagic Acid
## 5 Conclusions  
In recent decades, a growing interest in the administration of polyphenolic compounds for prevention of several diseases has arisen, since epidemiological studies have revealed a correlation between dietary habits and disease risks. In particular, EA exerts various health-promoting activities, suggesting that it may play an important role in dietary supplements. Furthermore, a few research studies proved that EA is endowed with a wide spectrum of therapeutic effects against oxidation-linked chronic illnesses such as, above all, diabetes, cancer, neurodegenerative disorders, and cardiovascular diseases. Unfortunately, EA presents unsuitable biopharmaceutical features, including poor bioavailability and interindividual variability that hamper its successful employment in prophylaxis and disease treatment. To date, on the market, EA is present in beverages, capsules, and tablets, which obviously do not overcome the problems associated with low oral EA intake; furthermore liquid formulation submits it to fast degradation. From this background, in order to address the many drawbacks associated with EA in vivo absorption, strategies mainly consisting of micro and nanotechnology approaches were designed and performed. The obtained EA formulations demonstrated modifying its release and improving its solubility, stability during storage, and bioavailability in animal models. However, from the evaluation of the various developed formulations, some considerations may be made. For example, approaches starting from basic EA solutions lead to higher EA content, but the preparation timing may represent a crucial factor as undesirable reactions such as oxidation and hydrolysis may occur. As a matter of fact, the choice of a proper vehicle for dissolving EA is challenging, because EA results rather insoluble in most common solvents. The attempt of reducing the size of EA powder through anti-solvent precipitation could be a recommended preliminary step as reported by different authors. Regarding micro and nanosystems preparative methods, encapsulation in biodegradable PLGA or PCL micro and nanospheres represents a valid route when effective EA protection, long circulation and controlled release are required, as, despite an initial burst effect, these systems provided a sustained release over one week. Thanks to its biocompatibility, chitosan was also extensively used, providing a rather fast EA release (50% within 8 h). Concerning lipid carriers, self-emulsifying systems are the most investigated ones, since they were usually endowed with high EA loading capacity and gastrointestinal release within 1 h. Although in the work of [PERSON] et al. food-grade excipients were used, the effects of surfactants concentration on intestinal epithelial integrity has to be taken into consideration. In this regard, it is of great importance to develop formulations with residual organic solvents or surfactants below the recommended maximum levels indicated by regulatory agencies. The most recent, innovative, and highly biocompatible EA formulations consisted of pectin spray dried dispersion, cyclodextrin-based nanosponges, zein nanocapsules, chitosan/alginate microspheres, lactoferrin/chondroitin sulfate nanoparticles, and supersaturatable self-microemulsifying delivery systems. With these promising advances, novel and more effective strategies could be applied for allowing extensive investigations on EA in vivo beneficial effects. In this regard, in the last pharmacokinetic study in humans, it was reported that after pomegranate extracts consumption, the key factors hampering EA effectiveness are: its low solubility at the gastric pH, its bounding to intestinal epithelium, the saturable transcellular transport and the interindividual variability to produce urolithins.