Lipid and polymeric nanocarriers for siRNA delivery to the brain

Brain diseases refer to any pathological conditions that impair the normal functions of the brain. These mainly include neurodegenerative disorders, brain injuries, and malignant tumors. Researchers have explored various therapeutic approaches to treat these conditions, with gene modulation gaining significant attention in recent years due to its potential to address the root cause of disease. One promising approach is the use of siRNAs as therapeutic agents for brain diseases. Most preclinical studies on siRNA delivery to the brain have employed invasive intracerebral methods to target specific brain regions, posing significant challenges for clinical translation. The challenges associated with the intracerebral route highlight the need for safer, more practical, and patient-compliant alternatives, such as systemic delivery. However, systemic siRNA delivery faces obstacles due to its inherent instability in circulation and the restrictive nature of the blood-brain barrier (BBB). Nanocarriers have emerged as a promising strategy to overcome these challenges. These nanocarriers can be made from various natural, synthetic, or biological materials, with polymers and lipids being the most commonly used due to their biocompatibility, ease of surface modification for targeting, controlled drug release, and improved stability. In this review, we discuss lipid- and polymer-based nanotechnology strategies aimed at overcoming the challenges of siRNA delivery and enhancing its therapeutic potential for treating brain diseases.