Insights into direct nose to brain delivery: current status and future perspective

Abstract

Now a day's intranasal (i.n) drug delivery is emerging as a reliable method to bypass the bloodbrain barrier (BBB) and deliver a wide range of therapeutic agents including both small and large molecules, growth factors, viral vectors and even stem cells to the brain and has shown therapeutic effects in both animals and humans. This route involves the olfactory or trigeminal nerve systems which initiate in the brain and terminate in the nasal cavity at the olfactory neuroepithelium or respiratory epithelium. They are the only externally exposed portions of the central nervous system (CNS) and therefore represent the most direct method of noninvasive entry into the brain. This approach has been primarily used to explore therapeutic avenues for neurological diseases. The potential for treatment possibilities with olfactory transfer of drugs will increase as more effective formulations and delivery devices are developed. Recently, the apomorphine hydrochloride dry powders have been developed for i.n. delivery (Apomorphine nasal, Lyonase technology, Britannia Pharmaceuticals, Surrey, UK). The results of clinical trial Phase III suggested that the prepared formulation had clinical effect equivalent to subcutaneously administered apomorphine. In coming years, intranasal delivery of drugs will demand more complex and automated delivery devices to ensure accurate and repeatable dosing. Thus, new efforts are needed to make this noninvasive route of delivery more efficient and popular, and it is also predicted that in future a range of intranasal products will be used in diagnosis as well as treatment of CNS diseases. This review will embark the existing evidence of nose-to-brain transport. It also provides insights into the most relevant pre-clinical studies of direct nose-brain delivery and delivery devices which will provide relative success of intranasal delivery system. We have, herein, outlined the relevant aspects of CNS drugs given intranasally to direct the brain in treating CNS disorders like Alzheimer's disease, depression, migraine, schizophrenia, etc.

Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases

“…Others have reviewed the intranasal delivery of a wide range of commercially available pharmaceuticals (13,16). They highlight some of the kinetics involved in determining the transport rate of the various drugs after intranasal delivery.…”

Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration

“…Recently, intranasal drug delivery is verified as a reliable method to bypass the blood-brain barrier (BBB) and deliver therapeutic drug to the brain and has shown therapeutic effects in both animals and humans (Mittal et al, 2014). Other researchers of our group have found that, either methotrexate or apomorphine after intranasal administration, the brain targeting index were significantly higher than other routes of administration (e.g.…”

Novel flurbiprofen derivatives with improved brain delivery: synthesis, in vitro and in vivo evaluations

“…Various strategies have been experimented to overcome the low brain permeability of CNS therapeutic agents (Kasinathan et al, 2014;Mittal et al, 2014). Prodrug strategy, one of the medicinal chemistry drug delivery systems, has been investigated extensively in order to increase the targeting efficiency of drugs to the brain (Anderson, 1996).…”