Background: The brain is the most protected organ in the human body; its protective shield, relying on
a complex system of cells, proteins and transporters, prevents potentially harmful substances from entering the
brain from the bloodstream but, on the other hand, it also stops drugs administered via the systemic route. To
improve the efficacy of pharmacological treatments, targeted drug delivery by means of polymer nanoparticles is
a challenging but, at the same time, efficient strategy.
Methods: Thanks to a highly multidisciplinary approach, several ways to overcome the brain protection have
provided effective solutions to treat a large number of diseases. Important advances in polymer science, together
with the development of novel techniques for nanocarrier preparation, and the discovery of novel targeting
ligands and molecules, allow a fine-tuning of size, shape, chemicophysical properties and surface chemistry of
functional particulate systems; it enables the improvement of the therapeutic performances for several drugs, also
toward districts that are difficult to be treated, such as the brain.
Conclusion: This review focuses on the great strides made from scientists and doctors in the development of
polymer nano-sized drug delivery systems for brain diseases. Even though the optimal nanocarrier was not yet
discovered, important advances were made to strive for safer, performant and successful systems, with the expectation
to find soon better solutions to cure some still untreatable pathologies.