: Blood-brain barrier (BBB) provides restrictions for the transportation of various therapeutic agents to the brain. Efforts to directly target the brain by olfactory as well as trigeminal nerve pathway, bypassing BBB, have grown significantly in recent times. The intranasal route of transportation of the drug encompasses ability for the delivery of drug directly to the brain, improves site-specificity in the brain and avoids systemic side effects. In the current era, novel drug delivery systems are useful tools for targeting the brain without providing any harmful effects in nasal mucosa as well as the central nervous system. The complex structure of nasal cavity, mucociliary clearance, degradation by the enzymes present in nasal cavity and pathological conditions like rhinitis, common cold, etc. are the major disputes for nasal drug delivery. The use of nanotechnological approaches like solid lipid nanoparticles, polymeric nanoparticles, nanoemulsions, liposomes and polymeric micelles provides the ability to overcome these barriers. There are several emerging nasal drug delivery technologies produced by various pharmaceutical companies to conquer these hurdles. This review tries to address the recent developments in the area of direct drug delivery to the brain through the nasal route.

Approximately 40 % drugs in the market are having poor aqueous solubility related problems and 70 % molecules in discovery pipeline are being practically insoluble in water. Nanocrystals is a prominent tool to solve the issue related to poor aqueous solubility and helps in improving the bioavailability of many drugs as reported in the literature. Nanocrystals can be prepared by top down methods, bottom up methods and combination methods. Many patented products such as Nanocrystals®, DissoCubes®, NANOEDGE® and SmartCrystals ®, etc., are available, which are based on these three preparation methodologies. The particle size reduction resulted into unstable nanocrystalline system and the phenomenon of Ostawald ripening occurs. This instability issue could be resolved by using an appropriate stabilizers or combination of stabilizers. The nanosuspensions could be transformed to the solid state to prevent particle aggregation in liquid state by employing various unit operations such as lyophilisation, spray drying, granulation and pelletisation. These techniques are well known for their scalability and continuous nanocrystal formation advantages. Nanocrystals can be characterized by using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy, powdered x- ray diffraction and photon correlation spectroscopy. The downscaling of nanocrystals will enable rapid optimization of nanosuspension formulation in parallel screening design of preclinical developmental stage drug moieties. One of the most acceptable advantages of nanocrystals is their wide range of applicability such as oral delivery, ophthalmic delivery, pulmonary delivery, transdermal delivery, intravenous delivery and targeting (brain and tumor targeting). The enhancement in market value of nanocrystals as well as the amount of nanocrystal products in the market is gaining attention to be used as an approach in order to get commercial benefits.