The biggest obstacle to the treatment of diseases that affect the central nervous system (CNS) is the passage of drugs across the blood-brain barrier (BBB), a physical barrier that regulates the entry of substances into the brain and ensures the homeostasis of the CNS. This review summarizes current research on lipid-based nanoparticles for the nanoencapsulation of neuroprotective compounds. A survey of studies on nanoemulsions (NEs), nanoliposomes/nanophytosomes and solid lipid nanoparticles (SLNs)/nanostructured lipid carriers (NLCs) was carried out and is discussed herein, with particular emphasis upon their unique characteristics, the most important parameters influencing the formulation of each one, and examples of neuroprotective compounds/extracts nanoencapsulated using these nanoparticles. Gastrointestinal absorption is also discussed, as it may pose some obstacles for the absorption of free and nanoencapsulated neuroprotective compounds into the bloodstream, consequently hampering drug concentration in the brain. The transport mechanisms through which compounds or nanoparticles may cross BBB into the brain parenchyma, and the potential to increase drug bioavailability, are also discussed. Additionally, factors contributing to BBB disruption and neurodegeneration are described. Finally, the advantages of, and obstacles to, conventional and unconventional routes of administration to deliver nanoencapsulated neuroprotective drugs to the brain are also discussed, taking into account the avoidance of first-pass metabolism, onset of action, ability to bypass the BBB and concentration of the drug in the brain.

Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non-toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and p-coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.

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