Biomedical nanovectors for the transport of antioxidants of natural origin

In recent times, research of natural antioxidants in various fields, such as cosmetics, food treatments and pharmaceuticals, are among the biggest challenges for industry and science. From a biomedical point of view, the strong scavenging power of reactive oxygen species (ROS) makes them functional tools for the treatment of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, Amyotrophic lateral sclerosis, Multiple Sclerosis. Their mechanism of action is based on the reduction of “oxidative stress”, a common characteristic of the above mentioned diseases. Hence, they prove to be a valid alternative to drugs currently used with limited performance. Antioxidants are a very large diversified family of molecules. Different classifications are reported according to nature (enzymatic or non-enzymatic), chemical-physical properties (hydrophilic or lipophilic) and structure (flavonoids, polyphenols, etc. In addition to the single isolated compound, the focus is on natural extracts characterized by an enormous variety of active antioxidant molecules within them. These favour a multitherapeutic effect for diseases with simultaneous contributions from different causes. The sources presented are curcumin, Ginkgo biloba, Grape, Olea europea L., Pomegranate, Ocimum sanctum, Nigella sativa, Salvia officinalis L, Tea, Berries and Ginseng. By the ease of extraction from food by-products and plant species, these antioxidants much more valued than artificial ones and other synthetic drugs. To this is added the lower toxicity and the lower price. Nonetheless, the limits linked to the poor accessibility of physiologically active doses, absorption, enzymatic destruction, rapid metabolism and excretion make nanotechnology-based strategies for their transport deeply attractive. This aspect is shared by natural extracts due to hypothetical solvent toxicity, low stability, low solubility of the bioactive compound. In addition, they must also overcome the greatest obstacle to the treatment of of central nervous system diseases: the Blood Brain Barrier. As the "guardian of the brain", it prevents the penetration of pathogens, toxins and most drugs and imaging agents with consequent peripheral side effects. The solution to considered problems is given by nanocarriers contributing to faster drug absorption, retention, targeted release at a specific site, the reduction of side effects. The protection of drug against degradation also allows a significant increase in its bioavailability, stability and improvement of pharmacokinetic properties. Significant examples of the results obtained for in vivo and in vitro studies and clinical trials are reported. The aim of the thesis is to demonstrate the powerful use of loaded antioxidants in new therapeutic solutions for the treatment of neurodegenerative diseases.