Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 18, Issue 34, Pages 5411-5420Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161212803307536
Keywords
5-Fluorouracil; Locoregional drug delivery; Oral squamous cell carcinoma; Buccal tablets; Tissue engineering; 3D oral outgrowths
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Funding
- MIUR, Rome
- MRC [G0800766] Funding Source: UKRI
- Medical Research Council [G0800766] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10021] Funding Source: researchfish
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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.
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