Depression is a life-threatening mental disorder and a major public health concern worldwide. It is associated with disability, reduced quality of life, significant health-related costs and a main risk factor for many other diseases. Current pharmacotherapeutic options exhibit limited efficacy and are associated with deleterious side effects. Efficacy of antidepressants is strongly dependent on their continued maintenance at the site of action (brain) over prolonged periods of time. Oral drug delivery is highly restricted by the existence of blood brain barrier, which demands the administration of high doses to ensure the access of therapeutic levels of antidepressant drugs to the brain, thereby resulting in a worsening of the side effect profile. This fact addresses a solid rationale for designing more effective dosage forms capable of directly transporting the drug to the brain to overcome the aforesaid drawbacks.
In this work, we have explored design considerations of lipid based nanoparticles for intranasal delivery of fluoxetine hydrochloride. In particular, nanostructured lipid carriers (NLC) and nanoemulsions (NE) were prepared using the hot high pressure homogenization technique. Formulations were suitably characterized in terms of colloidal and loading properties, rheological behaviour and stability. Finally, their performance in what concerns release and permeability was assessed through porcine nasal mucosa. Increasing the liquid lipid amount yielded a smaller particle size and respective distribution, and higher release rate. Conversely, NLC provided a superior permeability than NE, along with better stability profile, which pointed out these formulations as more appealing to fit an intranasal delivery of antidepressants.