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 delayed from 2.85 to 5.31 min at 140°C) with the increase in LLA/DLA block length ratio from 7 : 7 to 28 : 7 [266].
ABA triblock copolymer architecture is particularly useful for designing pressure sensitive adhesives (PSAs). The A‐ and B‐block usually comprised of glassy (minor, end component) and rubbery (major, central component), respectively. A‐block provide physical crosslinks and mechanical strength, while B‐block provide adhesion to the matrix. Commercial triblock copolymers adhesive properties could be improved by diluting entanglements in the central block. A‐block based on LA [267–269], γ‐methyl‐α‐methylene‐γ‐butyrolactone [270], and lactone acrylate [271] and B‐blocks based on β‐methyl‐δ‐valerolactone (βMδVL) [269] and ε‐decalactone (PDL) [268] sound promising from sustainability and degradability perspective. Copolymers based on LA with PDL or menthide‐based PSAs have also been reported because they can potentially degrade before or during the paper recycling process and simultaneously dilute entanglements and control viscosity, which are an essential criteria for their utility as PSAs [267]. An increase in the entanglement molar mass (M e) value was controlled by increasing the length of alkyl substituents in poly(n‐alkyl‐δ‐VL) without affecting the T g [272]. Recently, lactone sourced from cashewnut shell liquids (CNSLs)[273] seems to be promising sustainable approach being inexpensive, potentially degradable, and impart rubbery segment to affect rigidity of the block copolymer due to the presence of inherent long alkylene chain.
To impart surface hydrophilicity, porous scaffolds were successfully fabricated from copolymers of DXO, LLA, and ε‐CL through a solvent casting and particulate leaching technique, in which methanol was used to wet and swell the composite before leaching, thereby leading to an interconnected porous network. In the DSC thermograms of these copolymers, only a single T g located between corresponding copolymers was observed, indicating thereby a continuous amorphous phase due to the randomness of the copolymers [274]. In another approach, better hydrophilicity is achieved by surface functionalization of the porous resorbable scaffolds by covalent grafting [275].
4.6 DEGRADATION OF LACTIDE HOMO‐ AND COPOLYMERS
PLA and its copolymers especially when used for biological applications, besides requirement of optimization of mechanical properties by engineering at the molecular level, also demands a fast degradation polymer rate (less than usual reported time of a couple of months or years). A careful designing of polymer structure is required to optimize both these properties. To achieve a controllable degradation time of polymer demands exploration to satisfy various other desired parameters that are guided by end‐use application.
Hydrolysis of PLA under both alkaline and acidic conditions have been investigated. The presence of D‐lactoyl units reduces the hydrolysis rate [276]. The hydrolysis of copolymers of poly(LA‐co‐GA) was investigated at 37 and 60°C for 80 days. A three‐stage degradation was observed: during the first stage, the molar mass decreased rapidly with little mass loss; in the second stage, a severe mass loss was observed, and monomer formation was initiated; and in the third stage, via hydrolysis the oligomers were transformed to lactic acid and glycolic acid [277]. The GA units in the copolymers were hydrolyzed at a much faster rate than the LA units thus subsequently resulted in an increase in LA content in the remaining polymer.
Tacticity, nature, and length of sequencing in PLGAs found
