A drug delivery system for the paranasal sinuses consisting of a freeze-dried thermoresponsive hydrogel with degradable microspheres, called FD-TEMPS (Freeze Dried—Thermogel, Extended-release Microsphere-based delivery to the Paranasal Sinuses), was developed. Glass transition temperatures (Tg′) of the maximally freeze concentrated solutions consisting of poly(N-isopropylacrylamide) (pNIPAAm) and polyethylene glycol (PEG) were determined by differential scanning calorimetry, which informed optimization of the thermogel formulation. By replacing low molecular weight (MW) PEG (200 Da) with a higher MW PEG (2000 Da), the resulting freeze-dried gel exhibited a brittle texture, porous structure, and low residual moisture (< 3% measured by thermal gravimetric analysis). When combined with poly(lactic-co-glycolic acid) microspheres (PLGA MSs) and freeze dried, the complete system (FD-TEMPS) exhibited enhanced shelf-stability. Specifically, the smooth, spherical morphology of the MSs and initial release kinetics were maintained following 6 weeks of storage under ambient conditions. Furthermore, FD-TEMPS remained in place after application to a simulated mucosal surface, suggesting that it could be more uniformly distributed along the sinonasal mucosa in vivo. Freeze drying enables this delivery system to be stored as a ready-to-use product for better ease of clinical translation without compromising the thermoresponsive or sustained release characteristics that would enable local delivery of therapeutics to the sinonasal mucosa.
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The work was supported by not-for-profit funding received through the Eye & Ear Foundation of Pittsburgh. The authors would like thank Dr. Dan Lamont for assistance with the thermal analysis. The graphical abstract was created with Biorender.com.
The work was supported by not-for-profit funding received through the Eye & Ear Foundation of Pittsburgh.
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Schilling, A.L., Cannon, E., Fullerton-Shirey, S.K. et al. A ready-to-use, thermoresponsive, and extended-release delivery system for the paranasal sinuses. Drug Deliv. and Transl. Res. 12, 708–719 (2022). https://doi.org/10.1007/s13346-021-01069-3