title: Novel resveratrol and 5-fluorouracil coencapsulated in PEGylated nanoliposomes improve chemotherapeutic efficacy of combination against head and neck squamous cell carcinoma.
abstract: Increasing consumption of tobacco and alcohol has led to a steady increase in the incidence of head and neck cancers in Asia. The drawbacks associated with the existing chemotherapeutic and surgical interventions have necessitated the development of a safer alternative for therapy of head and neck cancers. In this study we have explored the synergistic therapeutic potential of a phytochemical and chemotherapeutic agent using PEGylated liposomes as a delivery vehicle. Resveratrol and 5-fluorouracil were successfully coencapsulated in a single PEGylated nanoliposome. The thermal analysis and the nuclear magnetic resonance results revealed that resveratrol localized near the glycerol backbone of the liposomal membrane while 5-fluorouracil localized closer to the phosphate moiety, which influenced the release kinetics of both drugs. The nanoformulation was tested in vitro on a head and neck cancer cell line NT8e and was found to exhibit a GI50 similar to that of free 5-fluorouracil. Further, gene expression studies showed that the combination of resveratrol and 5-fluorouracil exhibited different effects on different genes that may influence the net antagonistic effect. The coencapsulation of resveratrol and 5-fluorouracil in a liposomal nanocarrier improved the cytotoxicity in comparison with the free drug combination when tested in vitro.
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Aarti
authors.identifier: 0000-0001-6802-6854
authors.initials: A
authors.lastname: Mohan
authors.affiliation: AstraZeneca India Pvt. Ltd. Avishkar, Bellary Road, Hebbal, Bangalore 560024, India.
authors.forename: Shridhar
authors.identifier: 0000-0002-7781-7399
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Sethuraman
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Uma Maheswari
authors.identifier: 0000-0002-7163-3521
authors.initials: UM
authors.lastname: Krishnan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D000077185:Resveratrol; D000077195:Squamous Cell Carcinoma of Head and Neck; D013267:Stilbenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D013267:Stilbenes; D011092:Polyethylene Glycols; D000077185:Resveratrol; D005472:Fluorouracil