Abe and Tabata [242] demonstrated thermal properties and crystalline structures for a class of periodic aliphatic polyesters, with 3‐hydroxybutyrate and lactate units, can be varied over a wide range of temperatures based on stereosequence manipulations. Similarly, a statistical variation in chain microstructure found to affect various hydrolytic degradation rates in poly(lactide‐co‐ε‐caprolactone) matrices [243].
Besides modification in synthetic strategy, a variation in catalyst design is also exploited. Organocatalysts such as phosphazene‐based catalysts reported to form alternating PLGA with high regioselectivity and low dispersity [239]. Likewise, lactide‐based polymers, the nature of SC formation differs significantly between pure enantiomeric alternating copolymers to enantiomeric alternating LA‐based copolymers, poly(LLA‐alt‐GA)/poly(DLA‐alt‐GA) blends, as supported by WAXD and DSC [244].
4.5 PROPERTIES OF LACTIDE‐BASED COPOLYMERS
The physical properties and degradability of PLA copolymers can be easily controlled by changes in the polymer architecture by altering the structure of monomers and feed ratio to affect the composition of the repeat units, flexibility of the chain, inclusion of labile linkages, molar mass, crystallinity, and orientation of the backbone chains. Tong summarized the T g and T m of various aliphatic polyesters depending upon the tacticity and functionality present in the polymer [245]. Properties of PLA depend on the stereoisomers used for their preparation. PLLA and PDLA are semicrystalline hard materials with modulus of 2.7 GPa, tensile strength of 50–70 MPa, elongation at break of 4%, flexural modulus of 5 GPa, and flexural strength of 100 MPa [246–249]. The T m is around 180°C and T g is 60–65°C. The molar mass of the polymer, as well as degree of crystallinity, showed a significant influence on the mechanical properties [250–254]. Polymerization of a racemic mixture of 1 : 1 D,D‐LA and L,L‐LA or meso‐LA gave an amorphous polymer with a T g of 55–60°C and a tensile modulus of 1.9 GPa. The in vitro degradation of PLLA is much slower than PMLA (M = meso) due to its crystalline nature, and it takes two years for complete degradation of the former polymer. Surprisingly, a high crystallinity in the rac‐PLA is observed when polymerization of a racemic monomer in the presence of a racemic catalyst, a chiral Schiff’s base complex of aluminum was carried out [255]. This stereoselective mode of polymerization is accounted to the formation of stereocomplex as supported by powder X‐ray diffraction and NMR studies. Ovitt and Coates reported the formation of isotactic stereoblock PLA where each enantiomerically pure block contained an average of 11 LA units. The polymer showed a T m of 179°C, which is higher than that of the enantiomerically pure polymer suggesting the cocrystallization of the enantiomeric blocks of the polymer [199, 256].
PLGA copolymers are less stiff than the homopolymer, but are biocompatible, and undergoes hydrolytic cleavage yielding harmless products. Copolymer compositions containing 25–79% GA are found to be amorphous in nature because of the disruption of regularity of the polymer chain by the other monomer and are therefore interesting for drug delivery devices. The degradability of the copolymers depends on the composition of the backbone. An increase in the GA content from 15 to 50% decreased the degradation time from 5–6 months to 1–2 months. The morphology of the polymeric matrix showed a pronounced effect on degradation rate because ester hydrolysis proceeds more rapidly in the amorphous state [257].
The transition temperatures of the copolymers, T g (68–58°C) and T m (160–141°C), decreased with a decrease in lactoyl content from 90 to 70%. Polymers having LA less than 85% did not show a T m. The tensile stress at break of the PLGA copolymer films (M n value in the range of g/mol) decreased from 54 to 27 MPa with decreasing LA units from 90 to 70%. The elongation at break, however, increased with a decrease in LA content from 110 to 470% [18].
In biomedical applications, it is desirable to change the hydrophobic surface of PLGA to hydrophilic by surface treatments [258]. Some of these treatments include plasma discharge, corona discharge, and surface oxidation by chemical treatments [18, 258, 259]. Chemical treatment by 70% hydrochloric acid, 50% sulfuric acid, and 0.5 N NaOH resulted in a decrease in water contact angle of the surface from 73° to 60°, thereby showed an increase in hydrophilicity. The water contact angle for corona discharge and plasma discharge PLGA surfaces was in the range of 50–56° [20]. Such surface modifications resulted in an increase in adhesion, spreading, and cellular growth on the PLGA surface and may be helpful in improving the tissue compatibility of film and scaffold‐type substrates. Three‐dimensional PLGA porous scaffolds capable of controlled, sustained delivery using a foaming/particulate leaching method may be useful to regulate and enhance angiogenic factors (e.g., vascular endothelial growth factor) or gene transfer within a developing tissue [260, 261]. For example, amorphous PLGA copolymers having LA : GA ratios of 50 : 50, 75 : 25, and 85 : 15 foam to yield matrices with a porosity of up to 95%. PLGA 50 : 50 was found to be the most amenable to morphological changes during preparation of porous PLGA microparticles using a supercritical carbon dioxide pressure quench treatment of particles prepared using the conventional emulsion–solvent evaporation method [262].
In PLA‐b‐PEG copolymers, the LA blocks are hydrophobic while the EG blocks are soluble in water. As a consequence, such copolymers may form a micellar structure in water and are thus potential candidates for controlled drug delivery applications. The introduction of EG blocks in PLLA or PLGA copolymers increases flexibility and toughness. The T g of PLLA‐b‐PEG block copolymers showed a strong dependence on the composition and molar mass of the EG block [29]. A significant reduction in T g was observed by using high molar mass PEG or a high weight percent of PEG in the initial feed composition [263]. Microspheres based on poly(DL‐lactide) and triblock copolymers of PDLLA‐b‐PEG‐b‐PDLLA and loaded with λ‐DNA were prepared by a conventional solvent evaporation method based on formation of multiple w1/o/w2 emulsion. The degradation profile of these microspheres was quite different because of more swelling in the triblock copolymer due to the presence of the EG block. This swelling helped in maintaining a more stable condition for DNA and minimized initial burst release [25].
The poly(LLA‐b‐VL) copolymers having the monomers in the ratio 57 : 43 showed two endothermic transitions in DSC, representing the T m of the VL and LLA block, around 52 and 156°C, respectively. However, only one T m was observed in the block copolymers having higher ratio of one comonomer (e.g., LLA : VL = 19 : 81 and 81 : 19) [49]. Thermoplastic elastomers based on block copolymers having semicrystalline LLA terminal blocks and an amorphous heterogeneous middle block were prepared from DXO and TMC using a cyclic five‐membered tin oxide initiator. All the copolymers exhibited highly elastic behavior with a maximum stress at break of 35.6 MPa for a copolymer without DXO and maximum strain at break 1089% when the ratio DXO : TMC : LLA was 200 : 200 : 200 [264]. The mechanical properties of films of triblock copolymer based on LLA, DXO, and CL depend on the composition of the polymer backbone. Varying the composition of DXO, CL, and LLA in the copolymer varied the stress at break from 4 to 55 MPa and elongation at break from 25 to 1200% [265]. LLA/DLA block length ratio had a significant impact on the crystallization behavior of star‐shaped PPO‐b‐PDLA‐bPLLA stereoblock copolymers. The overall crystallization rate decreased (half time of crystallization