Engineering Particles and Polymers to Improve Pulmonary Therapeutics.

摘要

Pulmonary drug delivery has been an underutilized delivery space. Classically, pulmonary delivery has been employed for local delivery of small molecules for lung-centric respiratory diseases. The most typical example has been the application of corticosteroids as a treatment for asthma. There are multiple issues with this approach primarily focused on delivery as current formulations do not achieve a high amount of deposition into the lungs, which is countered by increased dose. To counter this, particle engineering strategies have been employed to improve delivery. By engineering our nanoparticle agglomerates, called NanoClusters, we have achieved increased deposition into the lungs. Corticosteroids are poorly water soluble and as such, dissolve slowly. There are lung clearance mechanisms that can clear these engineered NanoClusters before they dissolve, so the dissolution was assessed. It was observed that NanoClusters had enhanced dissolution making them an optimal system for lung delivery.;The lungs can be employed for regional and systemic delivery and not just local. The next study focused on delivery of a polymer, hyaluronic acid (HA) into the lungs. HA of different molecular weights was labeled, either fluorescently or with a radiolabel, and administered to mice. Labeled HA was tracked throughout the organs to determine the biodistribution of the polymer according to molecular weight along with determination of the pharmacokinetic parameters. The optimal size was determined to be between 67 and 215 kDa for HA to achieve increased persistence in the lungs. The lungs can be involved in the immune system as well in terms of systemic delivery. Recent research has shown that the lungs may contribute to profile switching in immune cells leading to different responses. By employing antigen presentation in a soluble antigen array for autoimmune diseases, there can be increased efficacy towards generating immune tolerance. By co-delivering two different antigens to the lungs, there is amelioration of the mouse model of multiple sclerosis suggesting the lungs may be a delivery space with increased possibilities in the future.