A series of copolymers of DLA and CL were synthesized by ROP using zinc lactate as a catalyst and carrying out the reaction at 145°C for 8 days. The formation of copolymers was confirmed by gel permeation chromatography (GPC), DSC and NMR. Interestingly, Kister et al. [53] used vibrational spectroscopy, particularly Raman spectroscopy, for determination of morphology, conformation, configuration, and composition of the copolymers. Raman spectroscopy thus appeared to be a suitable method for the identification of PDLA‐co‐PCL samples directly from solid samples without any special preparation.
Star‐shaped polymers consist of many linear polymers fused at a central point with many chain end functionalities. Owing to this exclusive structure, star polymers exhibit some remarkable characteristics and properties, which are unattainable by simple linear polymers [123]. Adapting a dual reaction mode strategy, i.e., ROP with click reaction allowed formation of miktoarm star‐shaped and inverse star‐block copolymers of CL with LA to design novel structures [124]. Recently, synthesis of optically active poly(lactic‐alt‐caproic acid) by cross‐metathesis polymerization (CMP) followed by hydrogenation is adopted, which is seemingly an attractive synthetic approach for designing alternating aliphatic polyesters [125].
4.2.5 1,5‐Dioxepan‐2‐One
Albertsson and coworkers [59, 60,62–64] reported extensive studies on copolymers of LA and 1,5‐dioxepan‐2‐one (DXO). Poly(1,5‐dioxepan‐2‐one) (PDXO) is a completely amorphous and hydrophilic wax‐like polymer with a T g of −39°C. When DXO is used as a comonomer with LA, it increases the hydrophilicity and rate of degradation of the copolymers as compared with PLA. The copolymers show characteristics of thermoplastic elastomers that are suitable for biomedical applications such as slowly degrading sutures, temporary implants, and drug vehicles. Although the synthesis of DXO was reported as early as 1972, Mathisen et al. [59] in 1989 described an improved reaction scheme with a high yield. The DXO block forms a soft amorphous block, while LLA block forms a hard‐semicrystalline segment in the triblock copolymer of poly(LLA‐b‐DXO‐b‐LLA) [60, 62, 63]. Blocks of controlled lengths were synthesized using a tin oxide initiator. Degradable polyesters with strictly defined structure, unique mechanical properties, and tuned degradation profiles were prepared and characterized [64]. The morphology of spin‐coated films of triblock copolymers poly(LLA‐b‐DXOb‐LLA) was characterized by AFM. These studies revealed the absence of nanoscale morphology in copolymer films [64].
4.2.6 Trimethylene Carbonate
Thermoplastic elastomers (TPEs) having unusual physical and chemical properties were prepared by copolymerization of LLA with TMC. Recently, a batch procedure for the preparation of degradable TPEs based on multiblock copolymers of LLA with TMC were reported [71] using a combination of ring‐expansion polymerization and ROP. The initiator used was 2,2‐dibutyl‐2‐stanna‐1,3‐oxepane. The block lengths were varied via the monomer/initiator and TMC/LLA ratio. These copolymers were transformed in situ into multiblock copolymers by ring‐opening condensation with sebacoyl chloride (Figure 4.9). Li et al. [126] developed the synthesis of a PLA/PPC [poly(propylene carbonate)] multiblock copolymer based on a one‐pot copolymerization of epoxides/carbon dioxide and LA using a ternary catalyst system that proceeds via an intermolecular chain transfer mechanism.
FIGURE 4.9 Representative structure of multiblock copolymers based on LLA and TMC [71].
4.2.7 Poly(N‐Isopropylacrylamide)
A block copolymer of N‐isopropylacrylamide (NIPAAm) and LA may combine the thermosensitive property of poly(NIPAAm) and the degradation of PLA. Micelles from such copolymers can improve protein release properties. Temperature change can alter the hydrophilicity and conformation of PNIPAAm, which may affect the physicochemical properties of micelles of the polymer. Amphiphilic block copolymers of NIPAAm and LA were prepared by first synthesizing hydroxy‐terminated PNIPAAm followed by ROP of LA in toluene using Sn(Oct)2 as a catalyst (Figure 4.10) [73].
Similar copolymers have recently been synthesized by ROP of LA using the two hydroxyl groups of S,S′‐bis(2‐hydroxyethyl‐2′‐butyrate)trithiocarbonate (BHBT). The triblock copolymers PLA‐b‐PNIPAAm‐b‐PLA were synthesized by ROP of LA initiated by BHBT followed by reversible addition–fragmentation chain transfer (RAFT) polymerization of NIPAAm with a centered trithiocarbonate unit as a RAFT agent [74]. Self‐organization of such amphiphilic block copolymers in aqueous solutions indicated the formation of vesicles. Stabilization of vesicles was attained by cross‐linking chain extension of the NIPAAm block using hexamethylene diacrylate [73]. Multifunctional micelles for cancer cell targeting, distribution, and anticancer drug delivery were prepared using poly(NIPAAm‐co‐methacrylic acid‐g‐DLA) and diblock copolymers [41].
FIGURE 4.10 Reaction sequence for preparation of PNIPAAm‐b‐PLA [72].
4.2.8 Alkylthiophene (P3AT)
End‐functionalized poly(3‐alkylthiophene) (P3AT), where the alkyl side chain of thiophene moiety contains either 6 or 12 carbons in length, was used as a macroinitiator for ROP of LA, thereby yielding rod‐coil block copolymers as shown in Figure 4.11 [127].
A semicrystalline block copolymer PLA‐b‐P3AT‐b‐PLA showed a tendency to phase segregate due to a self‐assembly process. Alkaline etching of LA blocks from the polythiophene matrix led to the formation of nanoporous templates, which is useful to generate ordered nanostructures. Other block copolymers can be prepared by combining 3‐(2′‐ethyl)hexylthiophene (3EHT) and LA using a change‐of‐mechanism polymerization technique that utilizes two controlled polymerization techniques. A Grignard metathesis (GRIM) reaction is used to polymerize 3EHT to form bromine‐terminated P3EHT, which is then end‐functionalized with a hydroxyl group through a Suzuki coupling reaction to form the P3EHT–OH macroinitiator. Subsequent controlled ROP of D,L‐LA using triethylaluminum results in the synthesis of P3EHT–PLA block copolymers [128]. It is unlikely to obtain complete functionalization of the P3EHT–CH2OH parent homopolymer with PLA, residual P3EHT in the reaction mixture was removed from P3EHT–PLA by selective precipitation in petroleum ether. Other block copolymers containing PEG and thiophene unit as 3‐hexylthiophene (3HT), 3‐dodecylthiophene (3DDT), and 3‐(2′‐ethyl)hexylthiophene (3EHT) blocks are also reported via azide‐alkyne coupling reaction [129]. Thienyl‐difluoroboron‐PLA have been synthesized and used to explore oxygen‐sensing capability based on phosphorescence [130].