Preparation of Reduction-Sensitive Branched Block–Statistical Copolymers for Controlled Drug Release via a Secondary in Situ Branching Reaction

Branched or hyperbranched polymers with a high degree of branching (DB) and a narrow polydispersity index (PDI) are highly desirable for biomedical applications because of the significant effect of molecular weight (MW), DB, and PDI on their cytotoxicity and delivery efficiency. Although either the self-condensed vinyl polymerization (SCVP) or copolymerization with a small molecular cross-linker has been repeatedly highlighted to be an efficient strategy with respect to (hyper)branched polymers, the preparation of a (hyper)branched polymer with simultaneously a high DB and a narrow PDI has been a significant challenge because an increased DB was usually accompanied by a broad PDI. For this purpose, a reduction-sensitive branched copolymer synthesized via a reversible addition–fragmentation chain transfer (RAFT) copolymerization of a reducible monomer–initiator double-head agent, 2-((2-((2-bromo-2-methylpropanoyl)oxy)ethyl)disulfanyl)ethyl methacrylate (BSSMA), and a divinyl cross-linker, ethane-1,2-diyl d...