The treatment of various central nervous system (CNS) diseases has been challenging, despite the rapid development of several novel treatment approaches. The blood–brain barrier (BBB) is one of the major issues in the treatment of CNS diseases, having major role in the protection of the brain but simultaneously constituting the main limiting hurdle for drugs targeting the brain. Nasal drug delivery has gained significant interest for brain targeting over the past decades, wherein the drug is directly delivered to the brain by the trigeminal and olfactory pathway. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research.

Introduction: Nasal drug delivery that exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain is being widely explored by pharmaceutical companies, for the delivery of challenging drugs. Low-molecular-weight and lipophilic drugs are effectively absorbed by the intranasal route for efficacious brain targeting; however, high-molecular-weight and hydrophilic drugs present challenges in intranasal delivery. Areas covered: The present review critically evaluates the physicochemical properties of drugs and formulation variables that influence brain targeting by the intranasal route. It also encompasses the influence of physiological factors of the nose that can influence absorption and the strategies utilized to increase nasal drug absorption. Expert opinion: The challenges of drug delivery to the brain can be overcome by chemical and pharmaceutical approaches; current research is focused on developing novel drug delivery systems for both local and systemic actions. Nose-to-brain targeting has vast potential for commercialization, as these systems allow the lowering of doses, by direct targeting of the active molecule that provides easy attainment of the effective concentration at the target site. Consequently, these systems are being explored for the delivery of biologically active molecules, to treat the ailments of the CNS and various proteins, amino acids and hormones.

Alzheimer's disease (AD) is a neurodegenerative brain problem and responsible for causing dementia in aged people. AD has become most common neurological disease in the elderly population worldwide and its treatment remains still challengeable. Therefore, there is a need of an efficient drug delivery system which can deliver the drug to the target site. Nasal drug delivery has been used since prehistoric times for the treatment of neurological disorders like Alzheimer's disease (AD). For delivering drug to the brain, blood brain barrier (BBB) is a major rate limiting factor for the drugs. The desired drug concentration could not be achieved through the conventional drug delivery system. Thus, nanocarrier based drug delivery systems are promising for delivering drug to brain. Nasal route is a most convenient for targeting drug to the brain. Several factors and mechanisms need to be considered for an effective delivery of drug to the brain particularly AD. Various nanoparticlized systems such as nanoparticles, liposomes, exosomes, phytosomes, nanoemulsion, nanosphere, etc. have been recognized as an effective drug delivery system for the management of AD. These nanocarriers have been proven with improved permeability as well as bioavailability of the anti-Alzheimer’s drugs. Some novel drug delivery systems of anti-Alzheimer drugs are under investigation of different phase of clinical trials. Present article highlights on the nanotechnology based intranasal drug delivery system for the treatment of Alzheimer’s disease. Furthermore, consequences of AD, transportation mechanism, clinical updates and recent patents on nose to brain delivery for AD have been discussed.