Lipid nanocapsules to enhance drug bioavailability to the central nervous system

The central nervous system (CNS), namely the brain, still remains as the hardest area of the human body to achieve adequate concentration levels of most drugs, mainly due to the limiting behavior of its physical and biological defenses. Lipid nanocapsules emerge as a versatile platform to tackle those barriers, and efficiently delivery different drug payloads due to their numerous advantages. They can be produced in a fast, solvent-free and scalable-up process, and their properties can be fine-tuned for to make an optimal brain drug delivery vehicle. Moreover, lipid nanocapsule surface modification can further improve their bioavailability towards the central nervous system. Coupling these features with alternative delivery methods that stem to disrupt or fully circumvent the blood-brain barrier may fully harness the therapeutic advance that lipid nanocapsules can supply to current treatment options. Thus, this review intends to critically address the development of lipid nanocapsules, as well as to highlight the key features that can be modulated to ameliorate their properties towards the central nervous system delivery, mainly through intravenous methods, and how the pathological microenvironment of the CNS can be taken advantage of. The different routes to promote drug delivery towards the brain parenchyma are also discussed, as well as the synergetic effect that can be obtained by combining modified lipid nanocapsules with new/smart administration routes.