Improving Topical Drug Delivery for Treatment of Chronic Rhinosinusitis

Project: Research project

Description

Chronic rhinosinusitis (CRS) affects over 11 million Americans each year at an annual cost of $8.6 billion. CRS is treated with topical medications and oral antibiotics, but failed response to medical therapy results in 257,000 surgeries annually. While surgery alters anatomy, it does not address the inflammatory mediators contributing to this disease. Oral antibiotic and anti-inflammatory medicines are therefore needed before and after surgery, but long-term use may not be feasible due to cost and systemic side-effects. Topical medications potentially deliver high concentrations of these drugs to nasal mucosa while minimizing systemic side-effects. However, these potent drugs often fail to help patients even after surgery, possibly due in part to insufficient drug delivery to affected areas. Furthermore, patient instructions for using topical drugs have not been studied in a CRS population, even though this medication is frequently prescribed for this population.
The long-term objective of the proposed research is to fundamentally improve CRS treatment by maximizing topical drug delivery in areas of the sinonasal cavity affected by CRS, potentially reducing the need for surgical intervention. In this project, we will focus on improving the use of the most common form of particulate drug delivery, aerosolized liquid formulations delivered by sprays and nebulizers. We will combine computational fluid dynamics (CFD) modeling with in vitro and in vivo experiments in a prospective clinical study to quantify aerosol particle delivery to target sites in the sinonasal cavities of CRS patients before and after functional endoscopic sinus surgery (FESS), the most frequent surgical treatment for CRS. Our central hypotheses are that (1) there are combinations of head positions, nozzle positions, and breathing techniques that increase target-site particle deposition (TSPD) (“optimal use conditions”) before and after FESS over TSPD obtained using physician recommendations for these factors (“current use conditions”), and (2) CFD-derived optimal use conditions will increase TSPD in vitro (in nasal replicas) and in vivo (in CRS patients) compared to TSPD under current use conditions. The proposed research is expected to develop instructions and specifications for improved use of nasal sprays and nebulizers that maximize target-site particle deposition. This information will help improve medical management of CRS, which may help reduce the number of CRS patients who require primary or revision surgery. In addition, this research will be the basis for a subsequent randomized, controlled, clinical trial that will measure clinical outcomes in CRS patients after maximal delivery of aerosolized topical medications.
StatusActive
Effective start/end date4/1/153/31/19

Funding

  • NIH National Heart, Lung, and Blood Institute (NHLBI)

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Pharmaceutical Preparations
Nebulizers and Vaporizers
Hydrodynamics
Therapeutics
Research
Anti-Bacterial Agents
Nasal Sprays
Costs and Cost Analysis
Nasal Mucosa
Aerosols
Reoperation
Nose
Population
Anatomy
Respiration
Anti-Inflammatory Agents
Randomized Controlled Trials
Head
Outcome Assessment (Health Care)
Prospective Studies