Nanotechnology Applications to Improve Solubility of Bioactive Constituents of Foods for Health-Promoting Purposes

Foods-derived multifunctional compounds, such as carotenoids, vitamins, phytosterols, polyunsaturated lipids, curcuminoids, flavonoids and polyphenols, in addition to the basic nutritional value, own extra health benefits and are considered \u201cpharmaceutical-grade nutrients\u201d better known as \u201dnutraceuticals\u201d. Similarly, phytochemicals from plants, characterized by analogous chemical structures, can be considered \u201cpharmaceutical-grade molecules\u201d. They could provide both diseases preventive actions and remarkable therapeutic benefits but, the efforts for identifying their mode of action and for applying them into food industry with health-promoting purposes, are often unsuccessful. Solubility is essential for a good absorption in the gastrointestinal tract and to achieve the systemic concentration necessary for an effective therapeutic activity, but the majority of these compounds are water-insoluble. Consequently, when ingested, they encounter many difficulties in crossing the diverse barriers to reach the bloodstream and to distribute to cells and tissues. Their absorption at gastric or intestinal level is troubled and in addition, they suffer from early degradation or fast metabolism, so rarely they manage to reach the site of action in therapeutically effective concentration and their clinical applications result strongly limited. Toxic excipients and harmful solubilizing agents were and are extensively used for solubilizing and delivering non-soluble bioactive chemicals (BACs) despite the resulting unpleasant side effects complained of by patients. During last decades, several new techniques, often resorting to nanotechnology, aiming at enhancing BACs solubility, at solving their pharmacokinetics drawbacks, at avoiding their early inactivation or fast metabolism, have been developed. On this background, the following chapter provides an overview concerning nanotechnology contribute and its technological advancements in \u201cmanufacturing\u201d nutraceuticals and phytochemicals in more bioavailable nanoparticles. In addition, it is reviewed the involvement of nanoscience in developing and enhancing food-grade solid nanosized materials to be used as BACs \u201ccontainers\u201d and \u201cvehicles\u201d either for their safe and effective oral administration, in the frame of medical treatments, or for achieving smart food ingredients to improve the quality and shelf life of nourishments

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)