Cynthia Bosquillon's presentation on strategies to increase drug retention in the lungs highlighted several key challenges and innovative approaches in the field. She began by addressing the primary issue: the rapid absorption of inhaled drugs into the bloodstream, which often leads to systemic adverse effects and high attrition rates during preclinical development. This problem results in a limited number of drugs available for inhalation therapy, with many respiratory diseases remaining poorly managed.
Bosquillon explained that the airway epithelium, which varies anatomically and physiologically between the upper airways and alveoli, serves as the main barrier to drug absorption. Conventional strategies to increase lung retention, such as decreasing drug solubility and delivering drugs as dry powders, have been applied with limited success due to issues like local irritancy and rapid clearance by mucociliary mechanisms.
She then discussed alternative strategies, including encapsulating drugs into lipidic or polymeric particles, conjugating drugs to decrease permeability, and exploiting biological mechanisms like drug transporters and lysosomal trapping. Various nanocarriers, such as liposomes and solid lipid nanocarriers, have shown promise in improving drug stability and targeted delivery, although they face limitations like low drug loading and deposition in the lungs.
Bosquillon also introduced Polyglycerol Adipate (PGA) as a new polymer for lung delivery applications. PGA can self-assemble into nanoparticles and has shown no toxicity in vitro and in vivo. Modifications to PGA have been made to increase its glass transition temperature, making it suitable for solid micro-size particle formulation.
In conclusion, Bosquillon emphasised the need for better understanding of the mechanisms driving drug retention in the lungs and the development of new materials and strategies to improve lung retention.
