Evaluation of natural compounds for inflammatory diseases and their improvement by nanoencapsulation in phospholipid systems

Pollution, poor nutrition, insufficient physical activity, and the use of tobacco and alcohol are the primary cause of most chronic and aging-related diseases. When an overload of these free radicals cannot be gradually destroyed by endogenous antioxidants, its accumulation generates a phenomenon called oxidative stress. This process negatively affects the equilibrium of local gut microbiota and leads to systemic oxidative damage of cellular biomolecules (lipids, proteins and nucleic acids), thus, playing a major role in the development of chronic and degenerative illness such as cancer, autoimmune disorders, aging, cataract, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. Beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) ensure the barrier function of intestinal membrane against pathogens; stimulate the host immune system; prevent food allergies and tumours; produce vitamins; metabolize cholesterol and other lipids; and enhance mineral bioavailability. Conversely, the overgrowth of deleterious bacterial species (e.g., some Clostridium) causes chronic and acute bowel diseases and influence the development of comorbidities associated with aging, cancer and degenerative diseases. Manipulation of the microbiota and microbiome holds promise as an innovative strategy to favorably promote or support the host health. Also, antioxidants play a key role in attenuate oxidative responses in local or systemic conditions and their beneficial responses have the potential to increase life expectancy. They are produced from normal cell metabolisms in situ or incorporated from dietary intake. Phenolic compounds are ubiquitous in plant species and are able to cope with oxidative stress, thus playing a key role in the protection of human health. Since the in vivo bioavailability of such molecules is usually limited by poor water solubility and high instability, their efficacy can be improved by incorporation in suitable nanocarries. Recently, new types of products based on natural molecules loaded in technological nanoparticles have been developed and proposed as integrative food, cosmetic and therapeutic formulations. Due to the high costs and complex preparation methods, such delivery systems are commonly applied in drug delivery with only few therapeutic formulations currently on the market. In addition, no cosmeceutical and nutraceutical products containing natural molecules are currently marketed though nanosystems. This target represents a new frontier in both cosmeceutical and nutraceutical fields, which can take advantage of natural resources to obtain food, cosmetic and nutraceutical products. Additionally, these highly performant phytonanoformulations could be specifically designed using only environmentally-friendly, scalable methods and biocompatible ingredients. In fact, nowadays there is a large demand for such natural, eco-green and beneficial products as alternative of traditional medicaments. Both nutraceutical and functional food markets have grown and are expanding worldwide as a consequence of a rising global consumer demand for all-natural functional ingredients by healthy conscious consumers. Taking into account these findings, in the present PhD thesis new and environmentally-friendly phospholipid vesicles have been developed and tested as carrier to the intestinal delivery of a potent natural antioxidant, the curcumin. Curcumin (CUR) is one of the most widely distributed flavonoids and has demonstrated to possess potent anti-oxidant, anti-inflammatory and anti-carcinogenic activities. It controls the formation of proinflammatory mediators, such as prostaglandins and leukotrienes. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. Curcumin was loaded in phospholipid vesicles especially designed for intestinal delivery.