Catherine Fromen, PhD
Tuning Degradation Rates of Dry Powder Hydrogel Nanoparticle Formulations to Drive Antigen-Specific Immune Responses in the Lung
Summary
If the events of 2020 have shown us one thing, it is the dire need to develop new therapeutic and prophylactic approaches for respiratory diseases. Development of efficient inhalable immunotherapies remains a far-off goal, challenged in part by the paucity of knowledge surrounding the physiochemical properties which dictate desirable interactions with lung antigen presenting cells (APCs). There remains a critical need to develop particulate formulations specifically for lung administration and identify the physiochemical features that lead to optimized lung immune responses. Recent preliminary lab data has suggested that APC longevity is intimately controlled by the amount and frequency of nanoparticle (NP) internalization, as well as the rate of the particle intracellular degradation. Building from this preliminary data, this project’s central hypothesis is that slowly degrading particulate systems provide enhanced adjuvant-like effects that sustain APC viability and activation for extended antigen-specific adaptive immune responses. To test this hypothesis, the Fromen lab has engineered a library of antigen-loaded NPs for dry powder administration with tunable degradation rate and surface charge. The role of NP degradation rate and surface charge has been quantified in murine models of prophylactic lung vaccination, with ongoing efforts in a model of tolerogenic lung allergy. The proposed studies will broadly improve fundamental understanding of APC interactions with NP therapeutics in the lung, advancing development of inhalable NP immunoengineering while simultaneously catalyzing the PI’s research portfolio in pharmaceutical design of respiratory therapeutics.
I am incredibly grateful for the support from the PhRMA Foundation, especially through the events of 2020. Receipt of the Research Starter Grant has been critical to ensuring and sustaining the successful launch of an important area of my research program, allowing us to pursue a high risk-high reward research project that will not only yield long-term scientific progress, but also has a significant personal impact in supporting my overall career goals.
