Disulfide-cleavage- and pH-triggered drug delivery based on a vesicle structured amphiphilic self-assembly

Abstract

Hydrophilic poly (acrylic acid) (PAA) and hydrophobic α-tocopherol succinate (TOS) were integrated via a two-step amidation with cystamine (Cys) as the linkage, and then the self-assembly of amphiphilic PAA-cys-TOS occurred in the aqueous solution of methotrexate (MTX), an anti-cancer drug, resulting a vesicle structured drug carrier. Since the disulfide (-S-S-) bridge of Cys is sensitive to glutathione (GSH) and the amide bonds in PAA-cys-TOS are sensitive to pH, disulfide-cleavage- and pH-triggered drug delivery was achieved with the amphiphilic self-assembly. Of particular interest was that the topography of the self-assembly varied remarkably during the triggered delivery, which was indicated by TEM results.

Keywords: Amphiphilicity; Glutathione; Multi-triggered drug delivery; Self-assembly; Vesicle structure.