期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 519, 期 1-2, 页码 145-156出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2017.01.020
关键词
Vitamin E; Vitamin E TPGS; Tocopherol; Tocotrienols; PEGylation; Characterization; Functional excipient; Anti-tumor activity
资金
- National Institute of General Medical Sciences of the National Institutes of Health [P20GM103424]
Vitamin E refers to a group of saturated tocopherol (T) isomers and the biologically more active unsaturated tocotrienol (T-3) isomers. PEGylated alpha-tocopherol, commercially known as Vitamin E TPGS, has been used as an emulsifier and therapeutic agent for children with vitamin E deficiency. Limited information, however, is available about the PEG conjugates of the tocotrienol isomers of vitamin E. The current work was therefore undertaken to synthesize and characterize the water soluble polyethylene glycol (PEG 350 and 1000) derivatives of T and T-3. Yield and the identity of the synthesized products were confirmed by H-1 NMR, mass spectroscopy, HPLC, and thermal analysis. The self-assembly of the PEGylated vitamin E isomers in water at critical micelle concentrations (CMC) was further confirmed by size, zeta, and Cryo-TEM image analysis. While stable at pH 7.4, PEG conjugates were found to rapidly hydrolyze at pH 1.2. Our data showed that PEGylated T3 isomers were significantly more active as inhibitors for P-glycoprotein than PEGylated T. The in vitro cytotoxicity of the conjugates was also tested against a large panel of normal and tumorigenic cells. Of the conjugates, gamma-T3PGS 1000 and delta-T(3)PGS 1000 were found to have the least toxicity against non-tumorigenic breast and pancreatic cell lines, which may be advantageous for its use as functional excipients in drug delivery. The results from the current work have demonstrated the feasibility of synthesizing PEGylated conjugates of vitamin E isomers and highlighted the potential use of these conjugates in drug delivery as functional and safer excipients especially for gamma-T(3)PGS 1000 and delta-T(3)PGS 1000 conjugate. (C) 2017 Elsevier B.V. All rights reserved.
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