There is a broad range of biological, chemical and physical hurdles for drugs to reach the brain.
Nanoparticulate drug delivery systems hold tremendous potential for diagnosis and treatment of brain disorders, including
the capacity of crossing the blood–brain barrier and accessing to the brain after systemic administration.
Thus, nanoparticles enable the delivery of a great variety of drugs including anticancer drugs, analgesics, anti-
Alzheimer's drugs, protease inhibitors, and several macromolecules into the brain. Moreover, nanoparticles may
importantly reduce the drug's toxicity and adverse effects due to an alteration of the body distribution. A very critical
and important requirement for nanoparticulate brain delivery is that the employed nanoparticles are biocompatible
and, moreover, rapidly biodegradable. Therefore, nanocarriers fabricated from natural polymers including
polysaccharides and proteins are particularly interesting. Meeting requirements such as low cytotoxicity, abundant surface functional
groups, high drug binding capacity and significant uptake into the targeted cells, natural polymer-based nanocarriers represent promising
candidates for efficient drug and gene delivery to the brain. The current review highlights the latest advances achieved in developing
drug-loaded polysaccharide and protein nanocarriers for brain delivery. The nanoparticles are discussed with respect to their formulation
aspects, advantages, limitations, as well as the major outcomes of the in vitro and in vivo investigations. Modification of the nanoparticle
surface with specific brain targeting ligands or by coating with certain surfactants for enhanced brain delivery is also reviewed. In addition,
the mechanisms of the nanoparticle-mediated drug transport across the BBB are also discussed in this review.