Drug delivery strategies of Geraniol via nose-to-brain for the treatment of neuronal disorders

Parkinson’s disease (PD) is a neurodegenerative disorder which affects 1% of people over 65 years. Neuroinflammation and mitochondrial dysfunction play a central role in the disorder progression. Therefore, anti-oxidants, promoters of neurotrophic factor expression and mitochondrial rescuers could prevent the disease progression. Geraniol (GER) is a natural compound with demonstrated anti-oxidant and neuroprotective activities in PD models. However, its activity is impaired by a fast metabolism following oral administration, with a half-life of about 12 minutes. To overcome this limitation, nose-to-brain administration is a promising strategy because it allows the direct delivery of drugs beyond the blood-brain barrier avoiding the first-pass metabolism. However, GER is highly volatile and irritant. Thus, an appropriate delivery system for its nose-to-brain administration is required. Two different strategies were developed in order to achieve a successful nose to brain delivery. The first one aimed the encapsulation of pure GER and GER prodrug in solid lipid nanoparticles (SLNs), while the second one, displayed here, yearns to complex GER with cyclodextrins (CDs). The inclusion complexes were designed in order to reduce GER volatility and to obtain long-term stable formulations as powders.