Presentation description

Eosinophilic Chronic Rhinosinusitis (eCRS), an endotype of CRS, is a type 2 inflammatory disease that persists in the sinonasal cavity, affecting approximately 4 million adults in the United States. Despite the long-term use of biologics and endoscopic sinus surgery (ESS) to manage eCRS, approximately 50% of patients remain recalcitrant. eCRS is characterized by sinonasal tissue eosinophils, which contain granules densely packed with tissue matrix-degrading inflammatory proteins, including eosinophil peroxidase (EPX). Our recent investigations demonstrate that EPX activity is associated with increased disease severity in eCRS. EPX can serve as a diagnostic biomarker for accurately identifying patients with eCRS and as a predictive biomarker for increased medication use after ESS. While biologics often fail, studies show that engaging Siglec-8 on eosinophils induces apoptosis and subsequently inhibits EPX release, providing insight into a potentially novel target for limiting eosinophil production and degranulation. Prevention of EPX secretion via Siglec-8 engagement on eosinophils and the neutralization of EPX-mediated inflammatory signaling with a small molecule inhibitor (EPXi) has the potential to result in effective eCRS disease mitigation. However, the eCRS tissue microenvironment remains poorly characterized. Thus, performing tissue characterization is pertinent for identifying target biomarkers to support our drug delivery hypothesis, which aims to increase the efficacy and efficiency of eCRS therapeutics This involves designing a mucus-penetrating nanoparticle with Siglec-8 targeting moieties and encapsulated EPXi, formulated in a nasal spray to target eosinophil-based compartments in the disease state.