Lipid-based nanocarriers for oral delivery of natural anticancer bioactive compounds: A comprehensive review on mechanisms and approaches.

The exponential increase in the number of people with cancer has led researchers from different fields to investigate new treatment strategies that include, on the one hand, the testing of new molecules, the understanding of the mechanisms of formation, proliferation and inhibition of the growth of malignant cells, and on the other hand the development of innovative nanoformulas administered by different routes, including oral route. The tumor-targeted therapy is an emerging strategy based on the use of nanodelivery systems for the selective targeting of cancer cells and their organelles. A wide variety of anticancer nanomedicines have been tested, of which lipid-based nanocarriers (LBNCs) have shown high performances, such as increasing oral bioavailability and improving the pharmacokinetic profile of orally administered chemoterpeutics. This study provides an overview of the results published in the last decade regarding the role of natural bioactive compounds loaded within LBNCs in the prevention and treatment of cancer. The involvement of dietary compounds in the main processes that take place in the evolution of cancer is highlighted, e.g., cellular signaling pathways, apoptosis, autophagy, angiogenesis, oxidative stress and the multidrug resistance effect. Also, the main physiological barriers of the gastrointestinal tract (pH and chemical composition of gastrointestinal fluids, intestinal mucus, intestinal epithelial layer, intestinal metabolism, etc.) and tumor barriers (vascular endothelium, interstitial fluidic pressure, extracellular matrix, tumor microenvironment) are analyzed. Finally, the main types of LBNCs loaded with natural anticancer bioactives, including nanoliposomes, niosomes, nanoemulsions, solid lipid nanoparticles, and nanostructured lipid carriers are discussed.