Libero Italo Giannola, Viviana De Caro, Giulia Giandalia, Maria Gabriella Siragusa, Carlo Paderni, Giuseppina Campisi and Ada Maria Florena Pages 109 - 117 ( 9 )
5-Fluorouracil (5-FU) is currently used for treatment of oral squamous cell carcinoma (OSCC). 5-FU is given by i.v. although the systemic administration is associated with severe toxic effects and no topical formulations of 5-FU for buccal drug delivery have been reported. In this study we would report the development of buccal tablets suitable for direct application of low-doses of 5-FU on cancer lesions. The topical administration could be effective on tumor area while systemic undesired side effects are avoided. Preliminarily, the limited tendency of 5-FU to cross the buccal tissue was established using reconstituted human oral epithelium (RHOE, in vitro) and porcine buccal mucosa (ex vivo) as mucosal models. The values of steady-state flux and permeability coefficient suggested the scarce aptitude of 5-FU to reach the systemic circulation. Matrix buccal tablets, were designed for 5-FU local delivery, developed and prepared. Release tests showed a highly reproducible Higuchian drug discharge. After tablet administration on buccal tissue specimens, the occurrence of histomorphological effects of 5-FU was highlighted. Apoptotic events were registered in all samples treated while only negligible amounts of 5-FU permeated the buccal membrane and reached the simulated plasma. The results suggest that loaded matrix tablets containing 5% of 5-FU could be a useful means in topical treatment of OSCC.
5-Fluorouracil, Locoregional drug delivery, Porcine buccal mucosa, Reconstituted human oral epithelium, Oral squamous cell carcinoma, Buccal tablets
Department of Chemistry and Pharmaceutical Technologies, University of Palermo, Via Archirafi 32,90123 Palermo, Italy.