Central nervous system (CNS) diseases constitute a set of challenging pathological conditions concerning diagnosis and therapeutics. For most of these disorders, there is a lack of early diagnosis, biomarkers to allow proper follow-up of disease progression and effective therapeutic strategies to allow a persistent cure. The poor prognosis of most CNS diseases is, therefore, a global concern, especially regarding chronic age-related neurodegenerative disorders, which are already considered problems of public health due to the increasing average of life expectancy. The difficulties associated with the treatment of CNS diseases are owed, at least in part, to very specific characteristics of the brain and spinal cord, when compared to peripheral organs. In this regard, the CNS is physically and chemically protected by the blood-brain barrier (BBB), which, while maintaining essential brain homeostasis, significantly restricts the delivery of most therapeutic agents to the brain parenchyma. On the other hand, regenerative properties of the tissue are lacking, meaning that a CNS insult resulting in neuronal death is a permanent phenomenon. Approaches for transposing the BBB aiming to treat CNS diseases, relying on specific properties of nanosystems, have been reported for therapeutic delivery to CNS without interfering with the normal function of the brain.
Here, researchers from the University of Coimbra, Portugal address the latest advances concerning the principles of such approaches, employing lipid-based nanoparticles and cell-produced exosomes as drug and nucleic acid delivery systems, and summarize recent example of applications in the context of neurological diseases. They emphasize major achievements obtained in preclinical studies and the trends identified by these studies to provide new prospects for further developments in this area, thus enabling us to move from the research realm to the clinical arena.
Multifunctional lipid-based systems used in the treatment of CNS disorders. These vehicles present two compartments, one hydrophobic and one hydrophilic, which confers them the ability to carry a variety of drug molecules. Vector targeting promotes the delivery of therapeutic molecules to the site of interest, which can be achieved through ligand coupling to confer cell specificity, and improved by the incorporation of polymeric compounds, providing them with stealthiness.