Considerations in Nasal Drug Delivery

Vaccines administered via subcutaneous or intramuscular injection provide a systemic immune response but typically cannot block pathogens from breaching the body’s mucosal barriers. The lymphatic system propagates the immune response throughout the body and is not able to provide the same protection to the mucosal tissues, the site of entry of an infectious pathogen.

To combat pathogens getting into the body through the mucosa, researchers have developed mucosal vaccines. Such vaccines are presented to the nasal membranes in the same way as pathogens. Delivery of a vaccine to the nasal mucosa stimulates an immune response locally. One of the challenges is to promote sufficient coverage and time in the proper proximity to the tissue and getting the vaccine across the protective mucus coating on the surface of the membrane. The second challenge is to get the vaccine through the epithelial barrier. The ultimate target is delivery of the vaccine to the nasal associated lymphoid tissues to be able to block an infection by pathogens. The overall objective is to elicit a strong immune response at the mucosa to prevent infiltration of a pathogen and subsequent infection all together.

Formulation constructs suitable for an intranasal spray have additional needs over and above those of other dosage forms of lyophilized preparations, such as injections. The fundamental requirements of stability are the same for both an intranasal spray and a parenteral for direct injection: Stability as a bulk solution, during storage in the dried state, as well as upon reconstitution prior to administration. The viscosity of the constituted solution may influence dispersion of the spray and depth of penetration into the nasal passageway. A constituted solution also needs to be at the proper pH and osmolarity, not only for stability of the vaccine but also for the mucosal and epithelial layers of the nasal passage.

The mucus on the surfaces of the nasal passage is constantly turning over to rapidly clear foreign bodies and protect the nasal membrane. That means that increasing residence time in the mucosa and promoting close proximity to the nasal membrane can influence effectiveness of the vaccine delivery. Excipients chosen for the formulation may also influence transport across the epithelial barrier to the lymphoid tissues.

The Target Product Profile and Critical Quality Attributes are unique for a nasal delivery product presentation. As mentioned, attributes such as residence time on the mucosal layer and suitability for contact with the epithelial cells of the membrane are unique requirements for nasal delivery. Each of these desired attributes can be influenced by the formulation construct. The selected excipients play an important role in the effectiveness of the distribution and uptake of the vaccine.