Introduction: Orally-administered antipsychotics are effective in the management of psychosis-related disorders although 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 avert peripheral ADRs by maximizing cerebral drug concentrations, and reducing drug levels in the periphery. However, there exist physicochemical challenges related to psychotropic drugs, alongside biochemical barriers associated with targeting the olfactory region. 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.
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. 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 may be the most effective and direct administration route for antipsychotic delivery to the central nervous system (CNS). This research is novel and has the potential to revolutionize the mode of delivery of neurological medicines to the CNS in the future.
Keywords: Adverse drug reaction; antipsychotics; intranasal; lipid; nanoparticle; nose-to-brain delivery; polymer; psychosis; schizophrenia.