A convenient scheme for synthesizing reduction-sensitive chitosan-based amphiphilic copolymers for drug delivery

A novel type of reduction-sensitive graft copolymers, chitosan-S-S-poly(ε-caprolactone) (CS-S-S-PCL, here -S-S- means PCL was conjugated onto chitosan backbone through disulfide linkage), was synthesized through a convenient route using dithiodipropionic anhydride (DTDPA) as a disulfide donor. Reaction of hydroxy-terminated poly(ε-caprolactone) (PCL) with DTDPA quantitatively yielded DTDPA functionalized PCL (PCL-S-S-COOH). The disulfide-containing polyester was regioselectively conjugated onto the hydroxy groups of chitosan under mild and homogeneous conditions, utilizing dodecyl sulfate-chitosan complexes (SCC) as an intermediate. The self-assembly and Doxorubicin (Dox) release behavior of the copolymers were investigated. Spherical micelles could be formed through self-assembly of CS-S-S-PCL in aqueous media. The reduction-sensitive behavior of CS-S-S-PCL micelles was investigated by using Dithiothreitol (DTT) as a reductive reagent. In the presence of 10 mM DTT, the micelles gradually lost their aggregation stability and were precipitated out after four days. In addition, the Dox release was accelerated when the micelles were treated with DTT. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012