title: Nanoemulsion enhances α-tocopherol succinate bioavailability in rats.
abstract: The vitamin E analogue, α-tocopherol succinate (α-TOS), has a broad anti-tumor effect. α-TOS can induce cancer cells apoptosis and suppress tumor growth by targeting mitochondria. Low bioavailability of α-TOS is the major problem encountered with formulation development. In our study, α-TOS nanoemulsion (α-TOS-NE) was demonstrated as a new drug delivery system of α-TOS to increase the bioavailability. MTT-based cytotoxicity assay and mitochondrial membrane potential (ΔY) were performed on human breast cancer cell lines MCF-7 and human oral epithelial cancer cell lines KB to evaluate in vitro anticancer efficacy of α-TOS-NE. In comparison with free α-TOS, α-TOS-NE exhibited a stronger cytotoxicity and decreased ΔΨ. Pharmacokinetic profiles of I.V. α-TOS-NE group, I.P. α-TOS-NE group, and I.P. free α-TOS group (7% DMSO/93% PEG) were drawn. First of all, nanoemultion (NE) enables the I.V. injection of α-TOS, make it possible to be an I.V. preparation. Second, compare to the I.P. free α-TOS group, I.P. α-TOS-NE group had a higher bioavailability. Thus, NE improved the strong anti-cancer efficacy of α-TOS while increasing its in vivo bioavailability in rats. In conclusion, our laboratory-made NE was a safe drug delivery system for clinical trials and could be a promising formulation for α-TOS by I.V administration.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, PR China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, PR China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, PR China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, PR China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, PR China; Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, PR China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, PR China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, PR China. Electronic address: tangjl430@hotmail.com.
authors.forename: Jingling
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D006801:Humans; D007624:KB Cells; D061986:MCF-7 Cells; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000031:analogs & derivatives*; D024502:alpha-Tocopherol / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D014810:Vitamin E; D024502:alpha-Tocopherol
keywords: Bioavailability; Cancer; Mitochondria; Nanoemulsion; α-tocopherol succinate