Much of our research focuses on the modulation of the innate and adaptive immune response through respiratory drug delivery approaches to treat a variety of local and systemic diseases. We are interested in the development of both nasal and orally inhaled drug products.
Inhaled Therapies for Mycobacterial Lung Diseases
Mycobacteria are ubiquitous pathogens which have caused infections in man since the beginning of civilization. Common causative agents of mycobacterial lung disease are Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium abscessus. Targeted pulmonary delivery of anti-mycobacterial drugs could provide a viable alternative to systemic (oral or intravenous) drug delivery, as it eliminates the requirement for plasma-to-lesion drug distribution and can instead be utilized to directly administer drugs to infected macrophages, pulmonary biofilms and abscesses, and granulomas. In the Brunaugh Lab, we utilize advance particle engineering techniques to improve drug penetration and accumulation in granulomas and intracellular compartments to kill persister bacterial populations and improve therapeutic outcomes. We are also interested in the development of novel host-directed therapies for mycobacterial infections by examining the role of the innate immune system in infection progression and determining how this might be modulated through targeted inhaled drug delivery of small molecules and biologics.
Delivery of Biologics to the Respiratory Tract
Biologics (e.g., proteins, peptides, nucleic acids, and cells) are being increasingly utilized for the treatment of disease based upon their targeted nature. However, compared to small molecules, biologics have unique requirements to ensure absorption, stability, and safety. This is especially so for the delivery of biologics to the airways via inhalation, as the high stress processes required for development of droplets/particles suitable for nose or lung deposition are often at odds with the fragile nature of these entities. Once deposited, numerous barriers must be considered and overcome for the drug payload to be delivered to its site of action, including dissolution and penetration through the mucus, avoidance of macrophage phagocytosis, limiting system absorption (in the case of local therapy) or promoting drug transportation beyond the respiratory tract. We are interested in developing and optimizing formulations for the delivery of biologics to the respiratory system, with a particular focus on the engineering and testing of muco-adhesive and muco-penetrative drug delivery systems for nasal/nose-to-brain and pulmonary administration.