DDL 2022 looked to the future of OINDP development

Following Pritchard’s talk, Daniel Duke of Monash University discussed one of the technical challenges in making the transition to the new propellants, namely the need to redesign actuators to accommodate flow differences for 152a and 1234ze compared to 134a. Duke described the development of models that may allow MDI developers to “tune” the design of the nozzle orifice in order to get the desired spray and droplet characteristics when changing propellants.

In his talk on “Carbon footprint impact on inhalers,” Christer Janson of Uppsala University proposed that reducing most MDIs with DPIs and reducing the need for SABAs either by replacing them with ICS/formoterol therapy or by improving asthma control would be a feasible way to significantly reduce carbon footprint, although he acknowledged that some patients would still need to use MDIs.

When asked about the impact of the plastics used in DPI devices, Janson said that he had not considered that factor. Session moderator Omar Usmani pointed out that the a single trip to the hospital for a patient who suffers an exacerbation due to switching to a DPI could wipe out any carbon footprint savings from the switch. In response, Janson cited a need for training patients on how to use the inhalers properly.

Learnings from COVID-19
In his discussion of myeloid cell responses in severe COVID-19, Leif Erik Sander described a study initiated at the beginning of the pandemic at the largest university medical center in Europe that was designed to identify risk factors for severe COVID.

One thing that they noted early on, he said, was that children, who tend to have more interferon and other immune molecules circulating in their blood than adults, were seemingly more resistant to developing severe COVID. In response to a question about how to turn adult immune responses into those of children, Sander noted that it is unclear how kids’ immune systems change when they reach adolescence but suggested that one area to explore might be the use of inhaled ligands to prime the innate immune system in the mucosa.

Another clear finding from the study, he reported, was that “A dysregulated myeloid cell compartment is a hallmark of severe COVID-19.” One major discovery was that the risk factors for severe COVID overlap with idiopathic pulmonary fibrosis, with certain types of pro-fibrotic macrophages accumulating in both diseases and interaction of fibroblasts and macrophages driving fibrosis. Furthermore, patients with COVID-19 associated ARDS did develop lung fibrosis.

The remarkable thing, Sander revealed, was that in patients who survived COVID-19 ARDS, the fibrosis resolved; and he suggested that if researchers can uncover the mechanism behind the clearing of the fibrotic lesions in the lungs of these survivors, it could lead to a successful therapy for the treatment of diseases like IPF.

In the Lung Diseases session, Anna Piras of the University of Pisa presented a talk on “Aerosolised Phosphodiesterase 3 Inhibitor Enoximone in the Treatment of COVID-19 Pneumonia: In Vitro Evaluations Supporting Clinical Evidence,” in which she described a study conducted at an Italian hospital which suggested that off-label use of nebulized Perfan enoximone, a PDE3 inhibitor, is useful in treating COVID-19 ARDS. She suggested that a formulation designed specifically for inhalation “would be very useful for the treatment of pulmonary pathologies.”

And in the Pat Burnell session, two students from the University of Hong Kong presented their dry powder formulation projects aimed at the treatment or prevention of SARS-CoV-2 infection. In the first, Harry Pan spoke about “Development of an Immunogenic Spray-Freeze-Dried Powder Vaccine Against SARS-CoV-2.” In the other, Han Cong Seow of the University of Hong Kong described his work in development of a nasal dry powder formulation of ranitidine bismuth citrate, which has demonstrated activity against SARS-CoV-2. His project involves mixing powders with two different particle sizes in order to deliver the ranitidine to both the nose and lungs simultaneously for the treatment of viral respiratory infections.