Antipsychotic nanomedicine: a successful platform for clinical use.

Abstract

Nanomedicine, the medical application of nanotechnology, has great potential to solve problems in medicine (i.e., to diagnose, treat and prevent diseases at cellular and molecular levels) [1]. The particle sizes of nanomedicines range between 1 and 1000 nm (1 μm), which include macromolecular materials, polymers, noble metals, carbon nanomaterials and inorganic nanoparticles. Mostly, diagnostic and/or therapeutic agents are adsorbed, entrapped, conjugated or encapsulated in nanomedicines for diagnosis and/or treatment [1–4]. The nanomedicines linked with targeting ligand(s) can bind with specific targets/receptors on the cell membrane for targeting/synergistic effects. Advanced nanomedicines are now being developed in order to target specific organelles within the cells [3]. The surface-modified nanomedicines (i.e., hydrophilic surfaces) using PEG or its derivatives in the size range of 100–200 nm are generally preferred in order to produce desirable or ideal in vitro/in vivo qualities, such as bioavailability enhancement, toxicity reduction, dose reduction, solubility enhancement, drug targeting and product stability [2–7]. The various adverse effects associated with antipsychotic agents are a great concern, and minimizing these side effects remains a challenge in drug delivery research [8–10]. The atypical antipsychotics, such as risperidone, paliperidone palmitate, haloperidol, olanzapine and clozapine have been predicted to exert their superior therapeutic action with fewer adverse effects compared with older antipsychotics, but their clinical use remains restricted to limited numbers of patients due to various adverse effects, such as weight gain, the development of diabetes and blood dyscrasias, among others. Indeed, dose reduction of antipsychotic drugs can be achieved by using nanomedicines of antipsychotic drugs. The administration of nanomedicines via the parenteral route has advantages such as the avoidance of first-pass metabolism, targeted drug delivery and sustained release. Here, the concept of parenteral administration is effective for haloperidol, in that 1.5–3 mg/day intra muscular therapy of haloperidol is equivalent to 6–12 mg/day oral therapy [10]. In recent years, cuttingedge developments in antipsychotic nanomedicine have shown their preclinical and clinical effectiveness for the therapy of psychotic disorders [9–11]. The development of antipsychotic nanomedicine for bioavailability enhancement, extended drug release, dose reduction and toxicity reduction has been claimed as a novel idea [8,10]. The most successful antipsychotic nanomedicine platforms include polymeric nanoparticles, solid lipid nanoparticles (SLNs), nanocapsules, nanoemulsions, drug nanocrystals and micelles. Since 2009, Invega Sustenna (Janssen Pharmaceuticals Inc., NJ, USA), a nanomedicine (nanocrystal) product, has been commercially available for the treatment of psychosis. It is administered once monthly as a depot intramuscular (long-acting) injection [9]. This article will focus on the importance of antipsychotic nanomedicines loaded with drugs such as risperidone, paliperidone palmitate, haloperidol, olanzapine and clozapine Antipsychotic nanomedicine: a successful platform for clinical use