Chapter 3 – Lipid nanoparticles as non-viral vectors for siRNA delivery: Concepts and applications

siRNA has recently emerged as a potential therapeutic tool for the treatment of a variety of human diseases, such as viral infection, cancer, cardiovascular and inflammatory disorders. Briefly, siRNAs are double-stranded RNAs formed by 21-23 nucleotides that are able to bind to and trigger the degradation of specific target messenger RNAs (mRNAs) through the silencing induced by the RNA-induced silencing complex. Compared with conventional therapeutics, it affords high specificity, resulting in improved efficacy and decreased side effects. However, many hurdles hamper the effective clinical application, including low intracellular delivery and poor in vivo stability. These drawbacks can be improved by the use of drug delivery systems as non-viral carriers of siRNA, which present important advantages over viral carriers, particularly the lower immunogenicity. Lipid nanoparticles are the most commonly reported type of drug delivery system for siRNA. They consist of vesicular systems, with an inner aqueous cavity, where siRNA can be loaded, surrounded by a lipid bilayer. This chapter will focus on the efforts that have been carried out to deliver siRNA loaded in lipid nanoparticles, highlighting the advantages, disadvantages, applications, clinical relevance, and future perspectives.