Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases

The blood-brain barrier (BBB) restricts the access of therapeutic agents to the brain, complicating the treatment of neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery to the central nervous system (CNS), the potential of nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, the surface of the nanocarriers can be modified with ligands that interact with the BBB, enhancing their uptake and penetration across the brain endothelium by different physiological mechanisms, such as receptor-or transporter-mediated transcytosis. This review seeks to provide an overview of active targeting in brain delivery, while highlighting the potential of functionalized lipid nanocarriers to treat brain diseases. Therefore, in the first sections, we discuss the importance of active targeting in CNS drug delivery, present the different ligands commonly used for functionalization, as well as summarize the state of the art of the most recent and relevant studies of surface-modified lipid nanosystems developed for neurological disorders. Lastly, challenges hindering clinical translation are discussed, and critical insights and future perspectives outlined. Although some limita-tions have been identified, it is expected that in the upcoming years these nanosystems will be an established approach.

Automated summary

The blood-brain barrier restricts the entry of therapeutic agents into the brain, posing challenges for the treatment of neurological diseases. Nanocarriers, such as lipid-based systems, have been explored to overcome this limitation and improve drug delivery to the central nervous system. By modifying the surface of nanocarriers with ligands that interact with the blood-brain barrier, their uptake and penetration into the brain can be enhanced. This review provides an overview of active targeting in brain drug delivery and highlights the potential of functionalized lipid nanocarriers for treating brain diseases.