Formulation strategies for nose-to-brain delivery of therapeutic molecules

Abstract The ministration for disorders of brain is still standing in front as a great challenge due to the existence of various formidable obstacles such as the blood–brain barrier and blood–cerebrospinal fluid barrier (BCSFB) that does not allow the entry of many drugs into the central nervous system (CNS) and serves as a major hurdle in effective delivery of therapeutics to the brain as well as maintaining therapeutic concentration of the therapeutic drug molecule for a prolonged period. A number of invasive and noninvasive modalities have been explored for effective delivery of pharmacologically active substances across the brain compartment. Among all of them, intranasal drug delivery has emerged as a potential route to enable the targeting of the molecules in a better and effective manner. The highly permeable vasculature of nasal mucosa makes this route feasible for drug delivery with by-passage of first-pass metabolism. Therefore formulations to be delivered via nasal route are gaining lots of attention for the delivery of drug/proteins/peptides/others with improved bioavailability as compared to oral route. A significant increment in the patent filling in this direction is itself evidence for the effectiveness of the targeting of therapeutic agents via olfactory/trigeminal neural pathways into the brain using novel approaches and devices. This chapter focuses on aspects and importance of nasal drug delivery, anatomy and physiology, drug pharmacokinetic profile and underlying mechanisms, range of intranasal drug delivery approaches, and their potential areas of applications along with the latest developments, evaluating both the scope and limitations of this strategy that impedes the translocation of drugs to the CNS.