Medium-term culture of primary oral squamous cell carcinoma in a three- dimensional model: effects on cell survival following topical 5-fluororacile delivery by drug-loaded matrix tablets.

Abstract

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal tablets were designed to deliver 5-FU locoregionally to the cancer lesions of the oral cavity. Tablets were prepared using a drug loaded matrix of acrylic/methacrylic acid copolymer containing 1% (w/w) of 5-FU and applied on 3D outgrowths. The drug release from tablets appeared to be sufficient to induce cell death as confirmed by transmission electron microscopy and enzymatic assay (TUNEL). After 120 h of treatment, when about 90% of the drug had been discharged from the tablets into the culture environment, 5-FU caused loss of cell-cell communications and apoptotic cell death. After 192 h, a complete disaggregation of the 3D oral outgrowths and the death of all the cells was observed. Buccal matrix tablets could be considered a promising new approach to the locoregional treatment of OSCC. Risks of systemic toxicity are avoided since very low drug doses are delivered.

• Authors: Giuseppina Campisi, Libero Italo Giannola, Alberto Fucarino, Antonella Marino Gammazza, Alessandro Pitruzzella, Vito Marciano, Viviana De Caro, Maria Gabriella Siragusa, Giulia Giandalia, Domenico Compilato, Stephen T Holgate, Donna E Davies, Felicia Farina, Giovanni Zummo, Carlo Paderni, Fabio Bucchieri
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 18 Issue 34 Pg. 5411-20 ( 2012) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 22632387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acrylates
• Antimetabolites, Antineoplastic
• Excipients
• Methacrylates
• Tablets
• methacrylic acid
• acrylic acid
• Fluorouracil

Topics

• Acrylates (chemistry)
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Cell Communication (drug effects)
• Cell Culture Techniques
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Delivery Systems
• Excipients (chemistry)
• Fluorouracil (administration & dosage, adverse effects, pharmacology)
• Humans
• Methacrylates (chemistry)
• Microscopy, Electron, Transmission
• Mouth Neoplasms (drug therapy, pathology)
• Tablets