Table 1.

Novel drug delivery system-based formulations of natural products for oral cancer.

Natural Products/Extract	Formulation Type	Dose/Conc.	Polymer Used	Bioavailability /In Vitro Release	Major Outcome	References
BRAs	Gel	Applied 10% (w/w) freeze dried black raspberry gel (0.5 g gel) four times/day for 6 weeks.	Noveon AA1 and Carbopol 971 polymers	NR	Reduced lesion size and microscopic histological grade in 35% of patients	[164]
Camptothecin	Polymeric nanoparticles	33–40 microg/mL	Cyclodextrin derivative chitosan	47–51% drug content	Increased oral bioavailability	[182]
	NE	NR	Poloxamer 188	NR	Overcame the solubility and stability	[183]
Curcumin	Mucoadhesive NPs	500 µg/mL	PCL + chitosan	NR	Improved bioavailability, decreased hydrolytic and photochemical degradation of curcumin	[176]
	Nanoniosomes	16 μg	NR	NR	Overcame poor oral bioavailability, enhanced drug stability	[161]
D9 –Tetrahydrocannabinol, Cannabidiol	Microspheres	(9 wt%- drug loading)	PCL	NR	Reduced tumor growth by enhanced apoptosis and decreased cell proliferation and angiogenesis	[169]
Genistein	NE	2 mg/mL	Chia seed oil, DL-a-tocopherol	NR	Enhanced anticancer drug partitioning to oral mucosal membrane, targeted delivery of Genistein at the site of action	[175]
Naringenin	NPs	50 mg	EE:PVA	High encapsulation efficiency of 88 ± 2.7%	More potent anti-lipid peroxidative, antiproliferative and antioxidant potentials	[134]
Paclitaxel	Mucoadhesive Sol-Gel system	0.2 mg	Thermosensitive polymer pluronic F127 and mucoadhesive polymer polyethylene oxide	90% of the drug over 3-day period; moreover, the release was sustained	Improved paclitaxel solubility, reduced toxicity	[184]
	Hydrogel	6 mg/mL	Chitosan	Drug release was found to be 32.3 ± 1.3% in 24 h and 61.7 ± 2.6% in 72 h	Tumor volume was reduced up to 89.1 ± 3.5%	[173]
	NPs	150–230 mg/m2 frequency: 2–4 infusions every 3 weeks.	Albumin	NR	Clinical and radiologic objective response in the majority of patients (78%). Intraarterial infusion of paclitaxel in albumin nanoparticles proved reproducible and effective	[185]
	Nanoliposomes hydrogel	300 μg/mL	Lipids [lipids containing soya phosphatidylcholile, nitro benzoxadiazol-labeled phosphatidylethanolamine]	NR	Exhibited greater cytotoxicity and provide a higher drug concentration	[170]
Resveratrol	NPs	5 µg/mL	PLGA-PEG-COOH	NR	Res-NP reduced the CSCs growth, metastasis, and angiogenesis by inhibiting the cytokines in CSCs enriched oral cancer cells niche	[138]
Rose Bengal	Si NPs	(For Preparation—o 400 microM RB)	Aerosol AT	NR	Enhanced phototoxicity by enhanced uptake	[145]
SIL	NPs	15 μg/mL	EE 100, PVA	24.1% of the entrapped SIL release in 6 h) (~79.2% of the drug released in 24 h	Enhanced cytotoxicity of SILNPs extensive DNA damage, increased MMP alteration	[156]
Garlic	Garlic extract-modified titanium dioxide NPs	10 mg/mL	NR	60.76%	Exhibited cytotoxic activity against oral cancer cell line by decreasing the cell viability; the production of ROS led to decrease in cell viability	[129]

Abbreviations: BRAs, black raspberry anthocyanins; CSCs, cancer stem cells; EE, eudragit E; MMP, mitochondrial membrane potential; NE, nanoemulsion; NPs, nanoparticles; PCL, polycaprolactone; PLGA-PEG-COOH, poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid; PVA, polyvinylalcohol; Res, resveratrol; ROS, reactive oxygen species; SIL, silibinin.