الفهرس 
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Abstract
Oral cancer is one of the leading causes of death worldwide. Oral precancerous lesions (OPL) are the
precursors of oral cancer, with varying degrees of progression. Tetrahydrocurcumin (THC) is a major
metabolite of curcumin with superior anticancer properties against various types of cancer. However,
THC’s clinical outcome is limited by its poor aqueous solubility. Herein, we developed novel mucoadhesive
biopolymer-based composite sponges for buccal delivery of THC, exploiting nanotechnology and
mucoadhesion for efficient prevention and treatment of oral cancer. Firstly, THC-nanocrystals (THC-NC)
were formulated and characterized for subsequent loading into mucoadhesive composite sponges. The
anticancer activity of THC-NC was assessed on a human tongue squamous carcinoma cell line (SCC-4).
Finally, the chemopreventive activity of THC-NC loaded sponges (THC-NC-S) was examined in DMBA
induced hamster OPL. The selected THC-NC exhibited a particle size of 532.68 ± 13.20 nm and a zeta
potential of −46.08 ± 1.12 mV. Moreover, THC-NC enhanced the anticancer effect against SCC-4 with an
IC50 value of 80 µg/mL. THC-NC-S exhibited good mucoadhesion properties (0.24 ± 0.02 N) with
sustained drug release, where 90% of THC was released over 4 days. Furthermore, THC-NC-S had a
magnificent potential for maintaining high chemopreventive activity, as demonstrated by significant
regression in the dysplasia degree and a decline in cyclin D1 (control: 40.4 ± 12.5, THC-NC-S: 12.07 ±
5.2), culminating in significant amelioration after 25 days of treatment. Conclusively, novel THC-NC-S
represent a promising platform for local therapy of OPL, preventing their malignant transformation into
cancer.