Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most common chronic disorders in nasal tissues. Main cause of nasal polypogenesis is the epithelial-to-mesenchymal transition (EMT) of the nasal polyp epithelium induced by hypoxia-inducible factor-1 (HIF-1). Topical administration of nasal drugs can decrease nasal polyp size and lessen sinonasal symptoms. However, treatments of nasal disease were complicated because of multiple physiological barriers which include flow of nasal mucous and epithelial cellular membrane. In this study, we propose a new strategy of delivering therapeutic reagents, inhibiting hypoxia induced HIF-1, into nasal epithelial cells as a conjugated form with a peptide for anti-nasal polyposis. The drug-peptide conjugate showed strong inhibitory effect against EMT at a concentration 20 times lower than that of free drug in respiratory epithelial cells. In nasal polyp mouse model, treating only submicromolar concentration of the conjugate showed much higher alleviation of polyp formation compared to the free drug. This system provides a new method for clinical treatment of chronic nasal diseases.

Peptide-mediated sinonasal delivery of therapeutic reagents for effective inhibition of epithelial to mesenchymal transition in nasal epithelium

2019 Fall National Meeting

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