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.

(1) Background: Clozapine is the most effective antipsychotic. It is, however, associated with many adverse drug reactions. Nose-to-brain (N2B) delivery offers a promising approach. This study aims to develop clozapine-encapsulated thermosensitive sol–gels for N2B delivery. (2) Methods: Poloxamer 407 and hydroxypropyl methylcellulose were mixed and hydrated with water. Glycerin and carbopol solutions were added to the mixture and stirred overnight at 2–8 °C. Clozapine 0.1% w/w was stirred with polysorbate 20 (PS20) or polysorbate 80 (PS80) at RT (25 °C) before being added to the polymer solution. The final formulation was made to 10 g with water, stirred overnight at 2–8 °C and then adjusted to pH 5.5. (3) Results: Formulations F3 (3% PS20) and F4 (3% PS80) were selected for further evaluation, as their gelation temperatures were near 28 °C. The hydrodynamic particle diameter of clozapine was 18.7 ± 0.2 nm in F3 and 20.0 ± 0.4 nm in F4. The results show a crystallinity change in clozapine to amorphous. Drug release studies showed a 59.1 ± 3.0% (F3) and 53.1 ± 2.7% (F4) clozapine release after 72 h. Clozapine permeated after 8 h was 20.8 ± 3.0% (F3) and 17.8 ± 3.1% (F4). The drug deposition was higher with F4 (144.8 ± 1.4 µg/g) than F3 (110.7 ± 2.7 µg/g). Both sol–gels showed no phase separation after 3 months. (4) Conclusions: Binary PS80-P407 mixed micelles were more thermodynamically stable and rigid due to the higher synergism of both surfactants. However, binary mixed PS20-P407 micelles showed better drug permeation across the nasal mucosa tissue and may be a preferable carrier system for the intranasal administration of clozapine.

Supercritical fluid (SCF) technology offers a potential green alternative to organic solvent-based methods for drug formulation. Albendazole (ABZ) has promising anticancer activity when formulated to increase its cellular uptake. Herein, a static volume method was used to determine the solubility of ABZ in supercritical carbon dioxide (scCO₂) for the future development of such ABZ formulations. The solubility of ABZ in scCO₂ (250 bar, 37 °C) was approximately 12 mg/100 mL. The extent of dissolution was measured at various time points to determine when saturation solubility occurred, which was demonstrated from 9 h. In order to determine if scCO₂ processing induced ABZ polymorphism, DSC/TGA, FTIR and XRD were used, which demonstrated no change in its solid state. Following this, ABZ loaded liposomes were manufactured using SCF technology. The liposomes diameter was 167.2 ± 5.3 nm as determined by Zetasizer, and confirmed by cryo-transmission electron microscopy. In conclusion, scCO₂ was used successfully to solubilize ABZ, and to manufacture liposomes of nano-sized range. This study provides insight into use of green technology for future ABZ liposomal formulation without the need for organic solvents. Graphical Abstract

Introduction: This study aimed to identify opportunities for clinical decision support targeting medication safety in remote primary care, by investigating the relationship between clinical workflows, health system priorities, cognitive tasks, and reasoning processes in the context of medicines used in people with chronic kidney disease (CKD). Methods: This qualitative study involved one-on-one, semistructured interviews. The participants were healthcare professionals employed in a clinical or managerial capacity with clinical work experience in a remote health setting for at least 1 year. Results: Twenty-five clinicians were interviewed. Of these, four were rural medical practitioners, nine were remote area nurses, eight were Aboriginal health practitioners, and four were pharmacists. Four major themes were identified from the interviews: (1) the need for a clinical decision support system to support a sustainable remote health workforce, as clinicians were “constantly stretched” and problems may “fall through the cracks”; (2) reliance on digital health technologies, as medical staff are often not physically available and clinicians-on-duty usually “flick an email and give a call so that I can actually talk it through to our GP”; (3) knowledge gaps, as “it takes a lot of mental space” to know each patient's renal function and their medication history, and clinicians believe “mistakes can be made”; and (4) multiple risk factors impacting CKD management, including clinical, social and behavioural determinants. Conclusions: The high prevalence of CKD and reliance on digital health systems in remote primary health settings can make a clinical decision support system valuable for supporting clinicians who may not have extensive experience in managing medicines for people with CKD.

The University of Queensland's institutional repository, UQ eSpace, aims to create global visibility and accessibility of UQ’s scholarly research.