Synthesis and Properties of Multicleavable Amphiphilic Dendritic Comb like and Toothbrush like Copolymers Comprising Alternating PEG and PCL Grafts

Facile construction of novel functional den dritic 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(m)B(n) dendritic comblike copolymers with alternating PEG (A) and PCL (B) grafts, and a subsequent chain extension polymerization of styrene, tert-butyl acrylate, methyl methacrylate, and N-isopropylacrylamide gave A(m)B(n)C(o) dendritic toothbrushlike copolymers. (PEG)(m)(PCL)(n) copolymers obtained were of adjustable molecular weight, relatively low polydispersity (PDI = 1.10-1.32), variable CTA functionality (f(CTA) = 4.3-7.5), and similar segment numbers of PEG and PCL grafts, evident from H-1 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(m)B(n) comblike copolymer. In vitro drug release results revealed that the drug release kinetics of the disulfide-linked A(m)B(n) 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.