This study used polymeric micelles to improve quality by increasing drug solubility, extending mucosal drug retention time, enhancing mucoadhesiveness, and promoting drug permeation and deposition. Fluocinolone acetonide (FA) was loaded into polymeric micelles (FPM), which were composed of poloxamer 407 (P407), sodium polyacrylate (SPA), and polyethylene glycol 400, and their physicochemical properties were examined. Small-angle X-ray scattering (SAXS) revealed a hexagonal micellar structure at all temperatures, and the concentrations of P407 and SPA were shown to significantly affect the solubility, mucoadhesion, release, and permeation of FPMs. The characteristics of FPM7 and FPM8 revealed crystalline states inside the micelles, which was consistent with the morphology and nano-hexagonal structure. The results of ex vivo experiments using focal plane array (FPA)-based Fourier transform infrared (FTIR) imaging showed that FPM7 penetrated quickly through the epithelium, lamina propria, and submucosa, and remained in all layers from 5–30 min following administration. In contrast, FPM8 penetrated and passed through all layers. FPMs with extended mucoadhesion, improved drug–mucosal retention time, and increased FA permeation and deposition were successfully developed, and could be a promising innovation for increasing the efficiency of mouth rinses, as well as other topical pharmaceutical and dental applications.
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