Nanosystems for targeted drug Delivery: Innovations and challenges in overcoming the Blood-Brain barrier for neurodegenerative disease and cancer therapy

The evolution of sophisticated nanosystems has revolutionized biomedicine, notably in treating neurodegenerative diseases and cancer. These systems show potential in delivering medication precisely to affected tissues, improving treatment effectiveness while minimizing side effects. Nevertheless, a major hurdle in targeted drug delivery is breaching the blood-brain barrier (BBB), a selective shield separating the bloodstream from the brain and spinal cord. The tight junctions between endothelial cells in brain capillaries create a formidable physical barrier, alongside efflux transporters that expel harmful molecules. This presents a notable challenge for brain drug delivery. Nanosystems present distinct advantages in overcoming BBB challenges, offering enhanced drug efficacy, reduced side effects, improved stability, and controlled release. Despite their promise, challenges persist, such as the BBB's regional variability hindering uniform drug distribution. Efflux transporters can also limit therapeutic agent efficacy, while nanosystem toxicity necessitates rigorous safety evaluations. Understanding the long-term impact of nanomaterials on the brain remains crucial. Additionally, addressing nanosystem scalability, cost-effectiveness, and safety profiles is vital for widespread clinical implementation. This review delves into the advancements and obstacles of advanced nanosystems in targeted drug delivery for neurodegenerative diseases and cancer therapy, with a focus on overcoming the BBB.