Controlling of free radical copolymerization of styrene and maleic anhydride via RAFT process for the preparation of acetaminophen drug conjugates

Abstract The presence of maleic anhydride moiety in styrene-maleic anhydride (SMA) copolymer makes it a versatile substrate for conjugation of drugs. In this study biocompatible styrene-maleic anhydride (SMA) copolymer with alternating structure was synthesized by gamma irradiation at room temperature in the presence of 2-phenyl-2-propyl benzodithioate (PPB). The poly(styrene- alt -maleic anhydride) (poly(St- alt -MA)) with narrow molecular weight distribution (Đ: 1.1–1.3) was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The synthesized poly(St- alt -MA) structure was characterized by ATR-FTIR spectroscopy, elemental analysis and 1 H NMR spectroscopy and molecular weight and dispersity were determined by size exclusion chromatography (SEC). SMA copolymers were further conjugated with acetaminophen via ester linkage and FT-IR, 1 H NMR investigation indicated that the acetaminophen was attached to poly(St- alt -MA). Drug release profile of the polymer-drug conjugate was followed by high performance liquid chromatography (HPLC). The drug-conjugate system was found to follow first order release kinetics with Hixson-Crowell model while drug release mechanism was found as non-Fickian diffusion after testing various kinetic models.