{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:08Z","timestamp":1790834468759,"version":"4.1.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Drug Deliv."],"abstract":"\n Background<\/jats:title>\n Oesophageal candidiasis remains challenging to treat owing to rapid transit of conventional oral formulations through the oesophagus, resulting in inadequate local drug delivery and reduced therapeutic efficacy. To address these limitations, the present study aimed to develop fluconazole-loaded chitosan microspheres (FCZ-CMs)-based orodispersible tablets (ODTs) that rapidly disintegrate in the oral cavity while releasing mucoadhesive microspheres capable of adhering to oesophageal mucosa, enabling sustained localized drug delivery.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n FCZ-CMs were developed by the emulsion cross-linking method using a 2\n 3<\/jats:sup>\n full factorial design to optimize particle size (PS), entrapment efficiency (EE), drug release (DR), and\n ex vivo<\/jats:italic>\n oesophageal retention (ORT). Optimised FCZ-CMs (F9) were extensively characterized by Infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and\n in vitro<\/jats:italic>\n drug release studies. Further, the ODTs developed by direct compression of F9 were evaluated for wetting time (WT), disintegration time (DT), drug content (DC), % drug release at 60\u00a0min (%DR), similarity (\n f<\/jats:italic>\n \n 1<\/jats:italic>\n <\/jats:sub>\n \/f<\/jats:italic>\n \n 2<\/jats:italic>\n <\/jats:sub>\n ), and stability under real-time and accelerated conditions.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The optimised FCZ-CMs (F9) exhibited a PS (31.81 \u00b1 1.14\u00a0\u03bcm), EE (84.12% \u00b1 2.15%), DR (58.46% \u00b1 1.89% at 60\u00a0min), and ORT (51.22% \u00b1 2.11% at 30\u00a0min), demonstrating excellent suitability for localized oesophageal delivery. FTIR confirmed drug\u2013polymer compatibility, SEM revealed spherical microspheres with a crenated surface morphology favourable for mucoadhesion, while DSC and XRD demonstrated reduced crystallinity of FCZ within the chitosan matrix. The ODTs loaded with F9 displayed high DC (99.14% \u00b1 0.58%), short WT (19.62 \u00b1 0.51s), and DT (23.83 \u00b1 0.86s). The dissolution profile of ODTs remained comparable to that of F9 (\n p &gt; 0.05<\/jats:italic>\n ), with drug release of 53.16% \u00b1 1.24% at 60\u00a0min and similarity factor (\n f<\/jats:italic>\n \n 2<\/jats:italic>\n <\/jats:sub>\n = 80) and difference factor (\n f<\/jats:italic>\n \n 1<\/jats:italic>\n <\/jats:sub>\n = 8<\/jats:italic>\n ), confirming that the compression process did not significantly alter the release behaviour of the optimised microspheres. The formulation also remained stable under both real-time and accelerated storage conditions.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The optimised ODTs successfully translated the performance of FCZ-CMs into a patient-friendly, oesophageal-targeted drug delivery system without compromising their controlled-release or mucoadhesive characteristics. The use of a simple, reproducible, and scalable direct compression process, together with preservation of microsphere functionality following tablet compression, highlights the translational potential of this platform for localized treatment of oesophageal candidiasis and deserves further clinical investigation.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fddev.2026.1962873","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:54Z","timestamp":1790833314000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and optimization of mucoadhesive chitosan microspheres for oesophageal delivery of fluconazole"],"prefix":"10.3389","volume":"6","author":[{"given":"H. 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