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

ABSTRACT

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

Article highlights

• The much-overlooked olfactory pathway may be the most effective administration route for antipsychotics, allowing direct access to the CNS with minimal systemic absorption.

• Direct N2B delivery of antipsychotics has the potential to substantially reduce peripheral ADRs by maximizing cerebral drug concentrations first, and reducing drug exposure to peripheral tissue.

• Lipid- & polymer-based nanocarriers present the most suitable platforms for enhancing the drug stability and bioavailability, enabling dose reductions of antipsychotics to minimize CNS and peripheral ADRs.

Declaration of interest

MSA Tan was supported by the UQ Research Training Scholarship from The University of Queensland. DJ Siskind is supported in part by an NHMRC ECF APP1111136. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.