Wednesday, May 21, 2025
5/21/2025
Subject specific modeling of drug absorption in nasal cavity - PROJECT SUMMARY/ABSTRACT Chronic rhinosinusitis (CRS) has a profound and negative impact on quality of life (QoL).1 Patients with CRS possess double the rates of depression, worse fatigue, and poorer sleep than control subjects.2,3 CRS is one of the most common chronic medical conditions worldwide, affecting all age groups. Its incidence is ~12.3% with an economic burden of greater than $60 billion annually in the US. Despite the substantial burden of CRS, sufficient treatment options have yet to be identified. While the reasons for developing CRS are incompletely understood, the underlying morbidity results from inflammation in the sinonasal cavity. Inflammation can be decreased by topical or systemic corticosteroid which blunt the adaptive immune response. While highly efficacious, systemic corticosteroids have many negative side effects including osteoporosis, mania, weight gain and hyperglycemia. To reduce adverse effects, topical intranasal corticosteroid sprays (INCS) are applied directly to the anatomic region affected while minimizing side effects; however, the efficacy of INCS is limited. Computational fluid dynamics (CFD) uses numerical methods to solve and analyze problems involving fluid flows. CFD has been used to help understand nasal airflow, effects of sinus surgery and INCS drug delivery. Current CFD models of INCS demonstrate that >90% of drug deposition occurs at the very front of the sinonasal cavity and does not reach the paranasal sinuses. However, we have recently utilized mass spectrophotometry to quantify INCS deposition in patients undergoing sinonasal surgery and found significant discrepancies between CFD models in silico and tissue deposition in vivo. This discrepancy between current CFD models and in vivo measurements is the result of static models that do not account for mucociliary clearance (MCC). The overall goal of this project is to enhance biomedical research capacity and opportunities for student research by developing a translational CFD program by creating a partnership between Morgan State University and The University of North Carolina. We will develop a novel CFD with both particle deposition and MCC in consideration for the drug absorption in nasal cavity, which will be validated by the in-vivo data for the first time: 1) Develop a translation CFD research program focused on nasal airflow and drug delivery; 2) Model drug intracellular absorption of INCS through mucous layer; 3) Model mucociliary clearance mediated drug movement in the nasal passage. This project will generate one key research deliverable: a robust CFD modeling tool to simulate the realistic drug absorption process in nasal cavity. Our team’s multidisciplinary approach will expand knowledge of drug absorption in nasal cavity, using well validated and responsible methodology to meaningfully enhance investigations in CRS. This project will also enrich the research capabilities in biomedical at Morgan State University as HBCU, provide high-quality research opportunities to students at HBCU, and contribute significantly to PI’s career development.
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