Branched copolymers were also synthesized by the preparation of macromonomers. Various types of methacrylate‐functionalized macromonomers are reported in the literature for the preparation of graft and star copolyesters. The reaction scheme used for the preparation of the macromonomers is depicted in Figure 4.15.
FIGURE 4.13 Synthetic route for the preparation of branched PLLA.
FIGURE 4.14 Reaction scheme of enzymatic polymerization [154].
FIGURE 4.15 Synthesis of macromonomers.
Segmented terpolymers of poly(alkylmethacrylate‐g‐DLA/dimethylsiloxane) were prepared by combination of a “grafting through” technique (macromonomer method) and controlled/living radical polymerization such as ATRP or RAFT. Different synthetic approaches for the ATRP synthesis of graft terpolymers can be adopted by either one‐step copolymerization or two‐step sequential approach. In a single‐step approach, the low‐molecular‐weight methacrylate monomer [methyl methacrylate (MMA), butyl methacrylate (BuMA)] (Figure 4.16) was polymerized onto a LA or dimethylsiloxane (DMS) macromonomer. The second strategy was a two‐step approach in which a graft copolymer containing one macromonomer is chain‐extended with the copolymerization of the second macromonomer and the low‐molecular‐weight monomer, forming a second block–graft copolymer [155].
FIGURE 4.16 Structure of LA‐ and DMS‐based macromonomers and macroinitiators (M: methacrylate, A: acrylate) [155].
4.4.1 Graft Copolymers
As mentioned earlier, the macromolecular design of a polymer regulates its physico‐chemical properties. Advanced structures such as combs, brushes, ladders, and so on were synthesized to meet the vast demands from different targeted applications of such polymers. Several graft copolymers based on LA are prepared to modify the properties such as degradability, transition temperatures (T g and T m), morphology, mechanical properties, and solubility. Surface characteristics of PLA films were modified by grafting. Micelle structures, having a multifunctional core and hydrophobic shell, were developed with higher drug activity and lower material toxicity. Some of these modifications are described in the following text. The star‐shaped highly branched polymers are discussed separately in Section 4.4.1.
To prepare degradable polymers, graft copolymers of LA acting as macromonomer and t‐butylacrylate were prepared by free radical polymerization. An increase in LA units resulted in an increase in the degradation rate [156]. ATRP of MMA (96.5%) and (meth)acrylate‐terminated LA‐based macromonomer (M n 2800 g/mol, 3.5%) yielded a homogeneously branched poly(MMA‐g‐LA) of low dispersity (Đ = 1.15) [157]. The reactivity ratio of MMA for conventional radical polymerization is 1.09 while with ATRP is 0.57. This accounted for the lower dispersity of ATRP‐synthesized poly(MMA‐g‐LA).
Degradable comb‐like polymer can be prepared by free radical copolymerization of LA‐based macromonomer with vinyl (N‐vinylpyrrolidone) and acrylic [MMA, methacrylic acid (MA)] monomers [158]. ROP to form PLA is not limited to synthesis of polymer and then fabricate or apply for specific purpose. Even PLA growth can be initiated at the surface via surface‐anchored poly(2‐hydroxyethyl methacrylate) (HEMA), which can then initiate ROP of LA using Sn(Oct)2 as a catalyst. An overall “bottle‐brush” structure of the polymer was obtained due to the formation of surface‐anchored poly(hydroxyethyl methacrylate‐g‐LA) [159].
PLA and its random copolymer with GA are grafted onto poly(vinyl alcohol) to increase hydrophilicity and manipulate the structure [160]. A novel comb‐type PLA was prepared using a depsipeptide–lactide random copolymer having pendant hydroxyl groups as macroinitiator for graft polymerization of LA. The comb‐type polymer had a lower T g, T m, and crystallinity than linear PLA [161].
A graft copolymer of poly(NIPAAm‐co‐methacrylic acid)‐g‐DLLA, [poly((NIPAAm‐co‐MAAc)‐g‐LA)], along with diblock copolymers of DLLA and EG and poly(2‐ethyl‐2‐oxazoline) was used for the formation of mixed micelles with a multifunctional core and core/shell morphology. These micelles exhibited higher drug activity and lower material cytotoxicity than micelles based on formulation without the inclusion of diblock copolymers [162]. This formation of nanostructure allowed screening of the highly negative charges (due to the carboxylic groups) in the pristine graft copolymer.
New thermoresponsive, pH‐responsive, and degradable nanoparticles comprising poly[DLA‐g‐(NIPAAm‐co‐methacrylic acid)] were prepared by grafting PDLA onto NIPAAm‐co‐methacrylic acid copolymer. A core–shell structure was formed with a hydrophilic outer shell and a hydrophobic inner core that exhibited a phase transition temperature above 37°C. The drug loading level of 5‐fluorouracil (5‐FU) as encapsulated nanoparticles from these copolymers could be as high as 20%. The release of 5‐FU was controlled by the pH in the aqueous medium. These studies indicated that these nanoparticles can be used as a drug carrier for intracellular delivery of anticancer drugs [163].
In biological systems, an organism can create the proper organic matrix as a substrate for the nucleation and growth of inorganic crystals due to the interfacial interaction between inorganic and organic phases. In analogy, in vitro fabrication of novel inorganic/organic composites holds special relevance in several biomedical fields more specifically in implants/bone regeneration. Such applications demand appreciable interactions at the interface of the two; demanding appreciable biocompatibility and favourable bioactivity to induce growth of bone cells. To provide abovementioned benefits, ceramics (hydroxyapatite) along with PLA modified with other functionalities such as carboxyl groups found to mediate the process. This interaction assisted the nucleation sites of HA crystals and may be used as a template to manipulate and control the growth and size of HA crystals necessary for bone growth. To affect the surface characteristics, photoinduced grafting appeared as a useful technique due to its usual advantages. Solvent cast PLA films were modified by grafting with vinyl acetate, acrylic acid, and acrylamide by a UV‐induced photopolymerization process [164]. For the same purpose, PLA surfaces have also been modified by grafting poly(methacrylic acid) via photooxidation followed by UV‐mediated polymerization. Thus, the introduced carboxyl groups due to MMA onto PLA surfaces acted as the nucleation sites of hydroxyapatite crystals. Nanohydroxyapatite/PLA composites with interfacial interaction between the two phases were prepared using these graft copolymers [165]. FTIR, XRD, and SEM studies supported that the modified PLA could act as a template to control the nucleation, growth, morphology, size, and distribution of hydroxyapatite crystals over the organic phase.
A thermoplastic polyolefin (TPO), more specifically TPO‐g‐PLA was prepared