Reductively degradable polyester-based block copolymers prepared by facile polycondensation and ATRP: synthesis, degradation, and aqueous micellization

Abstract

Well-defined reductively degradable amphiphilic block copolymers having disulfide linkages positioned repeatedly on hydrophobic chains, thus exhibiting fast degradation, were prepared by a combination of polycondensation and ATRP. The new method consists of three synthetic steps including, (1) polycondensation of commercially available diols and diacids through carbodiimide coupling or high temperature processes to synthesize degradable polyesters with disulfides labeled on the main chain at regular intervals (ssPES–OH), (2) bromination of ssPES–OH to ssPES–Br, and (3) ATRP for chain extension of ssPES–Br with water-soluble polymethacrylate, yielding ssPES-b-polymethacrylate block copolymers (ssABPs). The reductive cleavage of disulfide linkages in reducing conditions resulted in the degradation of ssPES homopolymers; their degradation rate was significantly enhanced with the increasing amounts of disulfide linkages in ssPES–OH and reducing agents. For ATRP, gel permeation chromatography and ¹H-NMR results confirmed the synthesis of well-defined ssABPs and revealed that polymerizations were well controlled. Because of their amphiphilic nature, ssABPs self-assembled in water toward the formation of core/shell micelles consisting of a hydrophobic ssPES core surrounded with polymethacrylate coronas. The effects of the corona's chain length on thermal properties and micellization in water of well-defined ssABPs were examined. Moreover, reductive (or thiol-responsive) degradation of ssABP-based micelles enabled fast release of encapsulated model drugs. Cell culture experiments confirmed nontoxicity and biocompatibility of well-defined ssABPs as effect candidates for targeted delivery applications.