title: PEGylated γ-tocotrienol isomer of vitamin E: Synthesis, characterization, in vitro cytotoxicity, and oral bioavailability.
abstract: Vitamin E refers to a family of eight isomers divided into two subgroups, tocopherols and the therapeutically active tocotrienols (T3). The PEGylated α-tocopherol isomer of vitamin E (vitamin E TPGS) has been extensively investigated for its solubilizing capacity as a nonionic surfactant in various drug delivery systems. Limited information, however, is available about the PEG conjugates of the tocotrienol isomers of vitamin E. In this study two PEGylated γ-T3 variants with mPEG molecular weights of 350 (γ-T3PGS 350) and 1000 (γ-T3PGS 1000) were synthesized by a two-step reaction procedure and characterized by (1)H NMR, HPLC, and mass spectroscopy. The physical properties of their self-assemblies in water were characterized by zeta, CMC, and size analysis. Similar physical properties were found between the PEGylated T3 and vitamin E TPGS. PEGylated T3 were also found to retain the in vitro cytotoxic activity of the free T3 against the MCF-7 and the triple-negative MDA-MB-231 breast cancer cells. PEGylated γ-T3 also increased the oral bioavailability of γ-T3 by threefolds when compared to the bioavailability of γ-T3 formulated into a self-emulsified drug delivery system. No significant differences in biological activity were found between the PEG 350 and 100 conjugates. Results from this study suggest that PEGylation of γ-T3 represents a viable platform for the oral and parenteral delivery of γ-T3 for potential use in the prevention of breast cancer.
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abu-Fayyad
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Fathy
authors.initials: F
authors.lastname: Behery
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Asmaa A
authors.initials: AA
authors.lastname: Sallam
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Saeed
authors.initials: S
authors.lastname: Alqahtani
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ebrahim
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: El Sayed
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Amal
authors.initials: A
authors.lastname: Kaddoumi
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sylvester
authors.affiliation: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Carroll
authors.affiliation: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Cardelli
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA; College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: nazzal@ulm.edu.
authors.forename: Sami
authors.initials: S
authors.lastname: Nazzal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D020285:Cryoelectron Microscopy; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D008970:Molecular Weight; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013499:Surface Properties; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan
keywords: Bioavailability; Cytotoxicity; PEGylation; TPGS; Tocotrienol; Vitamin E