# Biodegradable Polymeric Architectures via Reversible Deactivation Radical Polymerizations
## 2 Biodegradable Polymeric Architectures
### Well-Defined Star-Shaped Structures
After removal of trimethylsilyl-protecting groups the resulting pendent acetylene groups were then reacted with azide-functionalized linear polystyrene via a copper-catalyzed cycloaddition reaction between azide and acetylene functionalities. The \"brush-like\" arms could be cleaved via the hydrolysis of polyester star structure to generate molecular brushes. Combining RAFT polymerization with ATRP and hetero-Diels-Alder chemistry, [PERSON] et al. successfully prepared 12-armed star block copolymers. The biodegradable ester linkages between the arm and core confer the biodegradability to the generated polymeric architectures [65]. Star-shaped block copolymers with a biodegradable poly(lactide) core were also synthesized using RAFT polymerization combining copper-catalyzed Huisgen 1, 3-dipolar cycloaddition and thiol-ene Michael additions [66]. Figure 3: Synthesis of the star-block amphiphilic copolymer via ring-opening polymerization (**a**) and RAFT polymerization (**b**). Copyright 2010, Elsevier. Few star-shaped thermoresponsive polymers with six arms were prepared via RAFT polymerization by [PERSON]'s group. Star polymers with homopolymeric arms of poly(N-vinylcaprolactone) (PNVCL), copolymeric arms of poly(N-vinylcaprolactone- _co-N_-vinylpyrrolidone) (PNVCL-_co_-PNVP) and arms of block copolymers of poly(_N_-vinylcaprolactone- _b_-Vinyl acetate) (PNVCL-_b_-PVAc) and (PNVCL-_co_-PNVP)-_b_-PVAc were achieved by exploiting the R-RAFT synthetic methodology (or R-group approach), where the thiocarbonyl group is transferred to the polymeric chain end. Removing the xanthate group of the star polymers allowed for the introduction of specific functional groups at the ends of the star arms and resulted in an increase of the lower critical solution temperature (LCST) values. These star block copolymers could self-assemble into single flowerlike micelles, showing great stability in aqueous solution. Micellar aggregates of selected star polymers were used to encapsulate methotrexate showing their potential in the temperature controlled release of this antineoplastic drug (Figure 4) [67]. Figure 4: (**a**) Synthesis of hexafunctional star polymers and block copolymers based on PNVCL using amultifunctional xanthate as a RAFT agent; (**b**) Synthesis of star (PNVCL-_b_-PVAc)\({}_{6}\) copolymers; (**c**) Self-assembly in aqueous solution of star (PNVCL-_b_-PVAc)\({}_{6}\) block copolymers; (**d**) Synthesis of the star [PVAc-_b_-(PNVCL-_co_-PNVP)]\({}_{6}\) block copolymers. The blue and red colors represent PNVCL and PVAc, respectively. Copyright 2017, Elsevier. In another study reported by [PERSON] and [PERSON], the synthesis of selectively degradable core cross-linked star polymers using ATRP and ROP was presented [68]. In their study, both the arms and the core can be designed to be biodegradable and selectively degraded. The arms were also designed to be the same or different. The multifunctional initiator, 2-hydroxyethyl 2\({}^{\prime}\)-methyl-2\({}^{\prime}\)-bromopropionate was used to synthesize degradable poly(\(\varepsilon\)-caprolactone) (PCL) and nondegradable polystyrene (PSt) and poly(methyl methacrylate) (PMMA) macro-initiators, which were subsequently cross-linked to generate core cross-linked star (CCS) polymers. By using the non-degradable divinylbenzene (DVB) and ethylene glycol dimethacrylate (EGDMA) as well as the degradable (4,4\({}^{\prime}\)-bioxepanyl-7,7\({}^{\prime}\)-dione (BOD) and 2,2-bis(\(\varepsilon\)-caprolactone-4-yl)propane (BCP) monomers to cross-link the different macro-initiators, a range of CCS polymers were synthesized where either the arm or the core domain can be selectively degraded. Hydrolysis of PCL/PMMA/EGDMA miktoarm CCS polymer resulted in CCS polymer with a reduced number of arms, whereas PSt/BOD core-degradable CCS polymer yielded the original linear PSt arms upon hydrolysis. Similarly, [PERSON] et al.