Aerosol drug delivery through the mouth to target nasal cavities: RETRONOSE® concept




Nasal drug delivery is a non-invasive method that allows a rapid and high local therapeutic effect. It also offers significant opportunities for new drug development in order to deliver systemic drugs, vaccines and treatments for the central nervous system.

The clinical efficacy of a nasal treatment depends on its deposition in the nasal cavities, because the pharmaceutical target (local, systemic, vaccine, brain) is directly related to a specific nasal anatomical region. A study on chronic rhinosinusitis (CRS) patients has shown how corticosteroids deposition in the nasal cavities can have an impact on clinical outcomes [1]. This study has demonstrated the importance of a homogenous deposition in the different target regions of the nasal cavity, including maxillary sinuses to treat CRS. The turbinates, the maxillary sinuses and the ethmoid regions have been identified as important drug delivery target sites for local treatment of inflammation and infection in rhinological pathologies. Systemic delivery is enhanced by exposing the drug to the middle and inferior turbinates and the septum with a high vascularization and large surface area (around 150 cm2). The upper part of the nasal cavity (ethmoidal region) has been described as the target zone for nose to brain drugs [2].

Two main devices are on the market: Nasal spray and nebulizer. Nasal spray pumps are the more common devices used on the market for nasal drug delivery. However, they have limitations regarding their formulations and technologies. The drug fraction delivered beyond the nasal valve is low and most deposited drug is rapidly removed by mucociliary clearance and then eliminated through the digestive tract [3]. Furthermore, dose delivery to the target sites depends on many factors, such as nasal tip penetration and orientation, resulting in considerable variability in terms of drug deposition. Nebulizers are medical devices generating fine droplets. They produce a better penetration in the different parts of nasal cavities but they are associated with lung deposition and a duration of inhalation around 5 to 10 min which could limit the patient adherence. New devices are coming on the market for improving the deposition profile and all they use a nasal tip for drug delivery in the nose.

A different concept using a mouthpiece for aerosol drug delivery through the mouth to target nasal cavities has been developed. This new concept (RetroNose®) uses an aerosol generator to administer the drug through the buccal cavity during the nasal expiratory phase. The drug particles enter in the nasal cavities through the rhino pharynx. We have conducted different studies to evaluate the impact of this method on deposition profile in comparison with nasal drug administrated by a nasal tip.

In a first step, we evaluated the influence of the particle size, the expiratory flow rate and the anatomy on the deposition profile using nasal casts with RetroNose®.  In a second step, we compared deposition profile using nasal spray pump, nebulizer and a prototype based on the RetroNose® concept.