Synthesis and Properties of Multicleavable Amphiphilic Dendritic Comblike and Toothbrushlike Copolymers Comprising Alternating PEG and PCL Grafts

Abstract

Facile construction of novel functional dendritic copolymers by combination of self-condensing vinyl polymerization, sequence-controlled copolymerization and RAFT process was presented. RAFT copolymerization of a disulfide-linked polymerizable RAFT agent and equimolar feed ratio of styrenic and maleimidic macromonomers afforded multicleavable A_<i>m</i>B_<i>n</i> dendritic comblike copolymers with alternating PEG (A) and PCL (B) grafts, and a subsequent chain extension polymerization of styrene, <i>tert</i>-butyl acrylate, methyl methacrylate, and <i>N</i>-isopropylacrylamide gave A_<i>m</i>B_<i>n</i>C_<i>o</i> dendritic toothbrushlike copolymers. (PEG)_<i>m</i>(PCL)_<i>n</i> copolymers obtained were of adjustable molecular weight, relatively low polydispersity (PDI = 1.10–1.32), variable CTA functionality (<i>f</i>_CTA = 4.3–7.5), and similar segment numbers of PEG and PCL grafts, evident from ¹H NMR and GPC-MALLS analyses. Their branched architecture was confirmed by (a) reduction-triggered degradation, (b) decreased intrinsic viscosities and Mark–Houwink–Sakurada exponent than their “linear” analogue, and (c) lowered glass transition and melting temperatures and broadened melting range as compared with normal A_<i>m</i>B_<i>n</i> comblike copolymer. In vitro drug release results revealed that the drug release kinetics of the disulfide-linked A_<i>m</i>B_<i>n</i> copolymer aggregates was significantly affected by macromolecular architecture, end group and reductive stimulus. These stimuli-responsive and biodegradable dendritic copolymer aggregates had a great potential as controlled delivery vehicles