Synthesis, physiochemical characterization, and in vitro antitumor activity of the amide and pH cleavable hydrazone conjugates of γ-tocotrienol isomer of vitamin E with methoxy-poly(ethylene) glycol

Publication date: 30 August 2017 Source:International Journal of Pharmaceutics, Volume 529, Issues 1–2 Author(s): Ahmed Abu-Fayyad, Sami Nazzal The anticancer activity of water soluble methoxy polyethylene glycol (mPEG) derivatives of tocotrienol (T3) isomers of vitamin E was previously found to be reduced when compared to the parent free isomers. This could be due to the ester bond formation between the mPEG and the 6-OH group on the chroman moiety of the T3 isomer. To further investigate, the objectives of the current study were to (1) synthesize and characterize stable amide and cleavable hydrazone conjugates between mPEG and carbon-5 on the chroman moiety of T3, and (2) examine the cytotoxicity of the newly synthesized mPEG conjugates against breast (MCF-7 and MDA-MB-231) and pancreatic (BxPC-3 and PANC-1) cancer cells. Conjugates were synthesized by direct conjugation of succinyl chloride derivatives of mPEG to the α-tocopherol and γ-tocotrienol isomers of vitamin E, and were characterized by 1H NMR, FT-IR, and mass spectrometry. The micelles of the amide and hydrazone self-assembled conjugates were characterized for size, zeta, CMC, and stability at different pH media. The hydrolysis of the hydrazone conjugate was pH dependent with highest release at acidic (pH 5.5) conditions, whereas the amide conjugate was stable in all tested media. The amide conjugate nonetheless showed greater cytotoxicity than the hydrazone conjugate, which suggested that maintaining solu...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research