# Biodegradable Polymeric Architectures via Reversible Deactivation Radical Polymerizations
## 2 Biodegradable Polymeric Architectures
### Well-Defined Star-Shaped Structures
As an extension, a six-armed star architecture with disulfide intra-linkages on each arm was also synthesized using \"core-first\" methodologies, where a six-armed RAFT agent was synthesized first by attaching the RAFT agent via its \(Z\)-group to a core that has six RAFT active sites, followed by the RAFT mediated polymerization [49; 60]. The PDIs of the six-armed star polymers with amphiphilic copolymer arms of poly(St-\(b\)-PEG-A) were less than 1.31 for the copolymers up to 80% conversion, indicating a well-controlled mechanism by RAFT. After cleavage in the presence of dl-Dithiothereitol (DTT), the PDI of the single-armed chains was measured to be 1.20 by GPC, in accordance with the successful living polymerization. It should be emphasized that a lower PDI is not necessarily indicative of instantaneous arm growth from all thiocarbonate sites [61], as the fragmentation of the initial RAFT functionality may not favor the initiating group (R-group). This may be a noticeable problem at very low conversions, but as conversion proceeds, and the main RAFT equilibrium is attained, this is unlikely to become a significant influence on the kinetics and/or architectures. In [PERSON]'s study, biodegradable star-shaped poly(\(\varepsilon\)-caprolactone) and poly(\(\varepsilon\)-caprolactone-\(b\)-L-lactide) (5 sPCL-\(b\)-PLLA) with five arms were synthesized by ring-opening polymerization (ROP) from an asymmetric core. Subsequently, a series of amphiphilic and double responsive star-block copolymers were synthesized by RAFT star polymerization of \(N\),\(N\)-dimethylamino-2-ethyl methacrylate (DMAEMA) from the star-shaped macro-RAFT agent, which was prepared by attaching 3-benzylsulfonylthiocarbonylthiocarbonylsulfonylpropionic acid (BSPA) to 5 sPCL-\(b\)-PLLA  
Figure 2: **(a)** Multi-armed RAFT agents with biodegradable disulfide intra-linkers: three-armed RAFT agent with \(R\)-group at the end of each arm; three-armed RAFT agent with \(Z\)-group at the end of each arm and six-armed RAFT agent with \(R\)-group at the end of each arm; **(b)** Post polymerization modification of the three-armed star polymers with RAFT active center at the end of each arm. Copyright 2009, American Chemical Society. using a simple two-step reaction sequence. GPC and \({}^{1}\)H-NMR measurements demonstrated the polymerization courses are under control. The molecular weight of 5 sPCL-\(b\)-PLLA-\(b\)-DMAEMA increased with increasing monomer conversion and the molecular weight distribution ranged 1.19-1.37. Spherical micelles with degradable core and pH and thermo-double sensitive shell were prepared from the aqueous medium of the amphiphilic star-shaped copolymers through a dialysis method. Both pH and thermal-responsive behaviors of the copolymer micelles in this study were investigated (Figure 3) [62]. In addition to the well-defined symmetrical multi-armed polymeric structures, biodegradable, penta-armed star-block copolymers were also synthesized via an asymmetric core by combination of ROP and RAFT polymerizations, where the five-armed macro-RAFT agent was prepared by ROP on each arm. To generate more complicated polymeric architectures, combined methods should be more effective [63]. [PERSON] and [PERSON] [64] synthesized the degradable polyester-based star polymers with a high level of functionality in the arms via the \"arms first\" approach using an acetylene-functional block copolymer macroinitiator. This was achieved by using 2-hydroxyethyl 2\({}^{\prime}\)-methyl-2\({}^{\prime}\)-bromopropionate to initiate the ROP of caprolactone monomer, followed by ATRP of a protected acetylene monomer, (trimethylsilyl) propargyl methacrylate. The hydroxyl end-group of the resulting block copolymer macroinitiator was subsequently cross-linked under ROP conditions using a bislactone monomer, 4,4\({}^{\prime}\)-bioxepanyl-7,7\({}^{\prime}\)-dione, to generate a degradable core cross-linked star (CCS) polymer with protected acetylene groups in the corona.