Exploring the Potential of Non-Viral Nanocarriers for Improving Blood-Brain Barrier Permeability to Enhance the Treatment of Brain Diseases

Brain diseases have become an important health problem worldwide, especially in the aging population, and their incidence and prevalence continue to increase. Despite remarkable progress in medical technology, the treatment of brain diseases still faces many challenges, especially limitations caused by the blood-brain barrier (BBB), which significantly hinders the delivery of therapeutic drugs to the brain. In recent years, non-viral nanocarriers developed by nanotechnology have shown great potential for crossing the BBB, and have attracted much attention due to their low immunogenicity, high biocompatibility and good targeting. In this paper, we review the basic structure of the BBB, properties of nonviral vectors, and the mechanisms of crossing BBB. Moreover, this review summarizes the main types of non-viral vectors-liposomes, polymeric nanoparticles, biomimetic materials, and inorganic nanomaterials-while addressing the main translational barriers, including low BBB permeability, poor systemic stability, nonspecific peripheral accumulation, manufacturing challenges, and limited clinical validation, and suggests future research directions.