# Biodegradable Polymeric Architectures via Reversible Deactivation Radical Polymerizations
## 2 Biodegradable Polymeric Architectures
### Micelles, Vesicles and Capsules
#### 2.4.1 Micelles  
Micelles generated from well-defined diblock copolymers of thermoresponsive poly(\(N\)-isopropylacrylamide-_co-\(N\),\(N\)_-dimethylacrylamide) blocks and biodegradable poly(d,l-lactide) blocks by the combination of RAFT polymerization and ROP were also prepared by [PERSON] et al. The biodegradable polylactide (PLA) cores conferred the degradability to the micelles at acidic condition (pH 5.0). A much similar work was carried out by [PERSON] et al. who fabricated micelles using a thermal responsive poly(\(N\)-isopropylacrylamide) block, thus drug release could be thermally controlled. The presence of polycarbonate (PCL) block makes the micelle biodegradable in biological environments [94]. In [PERSON]'s study, well-defined, novel, linear, biodegradable and amphiphilic thermo-responsive ABA-type triblock copolymers, poly(2-(2-methoxyoxy) ethyl methacrylate-_co_-oligo(ethylene glycol) methacrylate)-_b_-poly(\(\varepsilon\)-caprolactone)-_b_-poly(2-(2-methoxyethoxy) ethyl methacrylate-_co_-oligo (ethylene glycol) methacrylate) (P(MEO\({}_{2}\)MA-_co_-OEGMA)-_b_-PCL-_b_-P(MEO\({}_{2}\)MA-_co_-OEGMA)) (tBPs), were synthesized via a combination of ring-opening polymerization (ROP) of \(\varepsilon\)-caprolactone (\(\varepsilon\)CL) and RAFT polymerization of MEO\({}_{2}\)MA and OEGMA monomers. Thermo-responsive micelles were obtained through a self-assembly process of copolymers in aqueous medium. The hydrophobic drug of anethole was encapsulated in micelles through the dialysis method. The average particle sizes of drug-loaded micelles were determined by dynamic light scattering measurement. In vitro, the sustained release of the anethole was performed in pH 7.4 phosphate buffered saline at different temperatures. Results showed that the triblock copolymer micelles were quite effective in the encapsulation and controlled release of anethole. The vial inversion test demonstrated that the triblock copolymers could trigger the sol-gel transition which also depended on the temperature, and its sol-gel transition temperature gradually decreased with the concentration increasing (Figure 9a,b) [95]. Another issue arising with the particle delivered drug delivery is how to enhance the delivering efficiency. The unmodified particles are usually evenly distributed in the body, if this is the case side effect might happen. Therefore, achieving targeted drug delivery has attracted enormous interest. [PERSON] and coworkers prepared surface functionalized micelles using amphiphilic triblock copolymers of oligo(ethylenedylcol) acrylate (PEG-A) and styrene (St), poly(PEG-A)-_b_-poly(St)-_b_-poly(PEG-A) by RAFT polymerization using a new bifunctional RAFT agent, _S,S_-bis[\(\alpha\), \(\alpha^{\prime}\)-dimethyl-\(\alpha^{\prime\prime}\)-(2-pyridyl disulfide) ethyl acetate] trithiocarbonate (BDPET) [96]. These micelles were tailored with surface bound pyridyldisulfide (PDS) groups that are active to a free thiol group bearing model peptide, reduced glutathione, and a thiol modified fluorophore, rhodamine B, under mild reaction conditions (Figure 9c). It can be envisioned that, when these micelles are tailored with specific targeting molecules, the delivery efficiency should be greatly enhanced and the unwanted side effect can then be avoided. It is usually difficult to obtain the complicated polymer architectures using a single polymerization technique. Combining with organo-base catalyzed polymerization of L- or D-lactide [PERSON] and coworkers, using ATRP technique, prepared biodegradable poly(isoglycerol methacrylate)-\(b\)-poly(L- or d-lactide) copolymer as building block for fabrication of spherical and large superamolecular vesicles via self-assembly in aqueous medium [97]. In most cases, the micelle cores are employed as drug reservoirs, however some novel micelles based on biodegradable poly (L-glutamic acid)-\(b\)-polylactide with paramagnetic Gd ions chelated to the shell layer were also prepared as a potential nanoscale magnetic resonance imaging (MRI)-visible delivery system [98].