Inhaled drug delivery systems, be they in the form oral or nasal, span many available types of devices, the number growing by the day due to the rapid evolution of the field. The current products competing for dominance include dry powder inhalers, metred dose inhalers, and nebulisers.
Inhaled formulations require unique characteristics compared to most other formulations. This mostly comes down to the physical and aerodynamic diameter of the particles, the latter of which being the most important part of inhaled formulation. Ahsan used the analogy of a feather and hammer dropped in mid-air at the same height to explain how particles’ density and size determine their ‘flight path’ through the air.
Major challenges of inhaled formulations include drug loss in the mouth and throat, mucus and cilia barriers, alveolar macrophage clearance, and dose variability impacting systemic drug delivery. Therefore, formulation scientists must consider these limitations when designing inhaled drugs, especially when they are intended for systemic effect.
Ahsan then introduced pulmonary atrial hypertension (PAH), a rare, complex disease marked by increased pulmonary arterial pressure leading to right heart failure; current treatments are mostly injectable with limited inhaled options.
His team developed inhaled particulate drug delivery systems using nanoparticles and liposomes conjugated with a CAR peptide to target pulmonary vasculature, aiming to enhance drug retention and reduce systemic side effects. Preclinical studies showed that CAR-conjugated liposomes increased drug accumulation in lungs, prolonged vasodilation, reduced pulmonary arterial pressure, and slowed right heart enlargement without affecting systemic blood pressure.
Fasudil, a vasodilator approved in Japan, and superoxide dismutase were reformulated for inhalation with improved pulmonary specificity; sildenafil inhalation extended vasodilatory effects compared to oral forms. Over 40 researchers have been mentored through this project, contributing to the advancement of inhaled therapies for PAH.
