Compatibility of a Thermoresponsive and Controlled Release System for Promoting Sinonasal Cilia Regeneration

The current clinical goal for managing chronic rhinosinusitis (CRS), a heterogenous disease of the paranasal sinuses, is to control inflammation, yet adjunct therapies that promote mucosal regeneration can improve the long‐term health of the upper airways. The small natural openings to the sinuses, however, limit the efficacy of traditional drug delivery methods (i.e., nasal sprays and irrigation). Accordingly, a conformable thermoresponsive and controlled release system (“TEMPS”, Thermogel, Extended‐release Microsphere‐based delivery to the Paranasal Sinuses) is developed. The poly(lactic‐co‐glycolic acid) microsphere component enables the encapsulation of numerous therapeutics, such as retinoic acid (RA), an analog of vitamin A (VA). Studies in CRS patients and preclinical models have shown that aqueous RA or VA gels promoted the differentiation of ciliated cells and improved mucosal healing following repeat applications. In the present study, TEMPS is designed for the controlled release of RA such that a single dose of RA‐TEMPS delivers bioactive drug for at least 30 days. Furthermore, as TEMPS will be in direct contact with sinonasal tissue, its compatibility with ciliated human nasal epithelium is explored. After ex vivo incubation in thermogel for 24 h, cilia motility is maintained, providing evidence that TEMPS can be compatible for application along the sinonasal epithelium. A thermoresponsive hydrogel with embedded controlled release microspheres is designed for local delivery of retinoic acid, which can induce cilia differentiation and promote sinonasal mucosal healing. The delivery system provides 30 days of bioactive drug release and gels at physiological temperatures of the sinuses. Additionally, cilia motility of human nasal epithelial tissue is maintained following ex vivo incubation in thermogel.