Nose-to-brain delivery of antipsychotics using nanotechnology: a review.

Introduction: Orally-administered antipsychotics are effective in the management of psychosis-related disorders although class or generation-specific adverse drug reactions (ADRs) significantly hinder clinical outcomes, driven by issues such as patient non-compliance. Direct nose-to-brain (N2B) delivery of antipsychotics via the olfactory epithelium could go some way in averting peripheral ADRs by maximizing cerebral drug concentrations, and reducing drug levels in the periphery. Moreover, the antipsychotic dose to attain a therapeutic effect could be reduced by the N2B approach, through avoidance of the entire gastrointestinal tract and first-pass metabolism. However, there exist physicochemical challenges related to psychotropic drugs, alongside biochemical barriers associated with targeting the olfactory region of the nasal cavity that impede direct, N2B drug delivery. Nanotechnological approaches present a viable strategy for the development of intranasal antipsychotic formulations where drug stability, mucosal absorption and cerebrospinal fluid (CSF)-bioavailability can be optimized, paving the way for N2B delivery.Areas covered: This review explores the unique anatomical features of the nasal cavity as a pathway for antipsychotic drug delivery to the brain. Nanocarrier-based approaches to encapsulate antipsychotics, and enhance stability, absorption and bioavailability are explored alongside methods to fabricate nanoparticles for brain drug delivery. The aim of this review is to determine current knowledge gaps for direct N2B psychotropic drug delivery, and identify clinically acceptable strategies to overcome them.Expert opinion: The olfactory epithelium located on the roof of the nasal cavity may be the most effective and direct administration route for antipsychotic delivery to the central nervous system (CNS), as systemic absorption is minimal. This research is novel and has the potential to revolutionize the mode of delivery of neurological medicines to the CNS in the future.