5-Fluorouracil buccal tablets for locoregional chemotherapy of oral squamous cell carcinoma: formulation, drug release and histological effects on reconstituted human oral epithelium and porcine buccal mucosa.
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 histo-morphological 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.
Department of Chemistry and Pharmaceutical Technologies, University of Palermo, Via Archirafi 32, 90123 Palermo, Italy. litagian@unipa.it
Libero Italo
LI
Giannola
Viviana
V
De Caro
Giulia
G
Giandalia
Maria Gabriella
MG
Siragusa
Carlo
C
Paderni
Giuseppina
G
Campisi
Ada Maria
AM
Florena
D000278:Administration, Buccal; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D009061:Mouth Mucosa / Q000033:anatomy & histology / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy*; D010539:Permeability; D013552:Swine; D013607:Tablets / Q000008:administration & dosage*; D046509:Tissue Culture Techniques
D000964:Antimetabolites, Antineoplastic; D013607:Tablets; D005472:Fluorouracil