A thermoresponsive hydrogel system for long-acting corticosteroid delivery into the paranasal sinuses.

Affiliation

Schilling AL(1), Kulahci Y(1), Moore J(2), Wang EW(2), Lee SE(2), Little SR(3).
Author information:
(1)Department of Chemical Engineering, University of Pittsburgh, 940 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA, 15213, United States of America.
(2)Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, 1400 Locust Street, Suite 2100, Pittsburgh, PA 15219, United States of America.
(3)Department of Chemical Engineering, University of Pittsburgh, 940 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA, 15213, United States of America; Department of Bioengineering, University of Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15213, United States of America; Department of Clinical and Translational Science, University of Pittsburgh, Forbes Tower, Suite 7057, Pittsburgh, PA 15213, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America; Department of Immunology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, United States of America; Department of Pharmaceutical Science, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15213, United States of America. Electronic address: [Email]

Abstract

Delivering localized treatment to the paranasal sinuses for diseases such as chronic rhinosinusitis (CRS) is particularly challenging because of the small natural openings leading from the sinuses that can be further obstructed by presence of inflammation. As such, oral steroids, topical nasal sprays or irrigation, and surgery can be utilized to treat persistent sinonasal inflammation, but there exists a need for post-operative options for long-term steroid delivery to prevent disease recurrence. In the present study, a Thermogel, Extended-release Microsphere-based-delivery to the Paranasal Sinuses (TEMPS) is developed with the corticosteroid mometasone furoate. Specifically, the bioactive steroid is released for 4 weeks from poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly(N-isopropylacrylamide) (p-NIPAAm)-based hydrogel. The temperature-responsive system undergoes a reversible sol-gel transition at 34-35 °C such that it can be applied as a liquid at ambient temperature, conforming to the sinonasal epithelium as it gels. In a rabbit model of CRS, TEMPS was maintained in rabbit sinuses and effectively reduced sinonasal inflammation as characterized by micro-computed tomography and histopathology analysis. Ultimately, the combination of controlled release microspheres with a thermoresponsive hydrogel provides flexibility for encapsulating therapeutics in a reversible and conforming system for localized delivery to the sinuses.