Delivering siRNA using nanoparticles to the central nervous system

The incidence of central nervous system (CNS) diseases is expected to increase significantly in the 21st century due to an increase in lifespan and changing population demographics. The most challenging of the CNS diseases are cancer and neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Hungtington’s disease that are characterized by age-related gradual decline in neurological function and neuronal death. Fundamental difficulties limiting the development of novel therapeutics include crossing the blood-brain barrier, and targeting of drugs to specific tissues or cells within the CNS. With the discovery of RNA interference (RNAi)-based therapeutics to achieve specific silencing of genes in the nervous system, the necessity to overcome such obstacles has become even more urgent. Most preclinical and clinical studies regarding delivery of small interfering RNA (siRNA) to the CNS have utilized invasive, intra-cerebral delivery of siRNA to the targeted tissue. New methods must be developed in order to facilitate delivery of therapeutically significant quantities of siRNA to the CNS via systemic route so that the full therapeutic potential of siRNA can be realized. Thus, developing safe and effective tissue-specific delivery vectors, minimizing the off-target effects, and achieving distribution in sufficient concentrations at the target tissue with minimal side effects are the major goals. In this chapter, we will discuss nanoparticle-based siRNA delivery to the CNS and their potential application in CNS diseases.