Butanediamine (BDA)‐g‐PDLLA was synthesized by grafting maleic anhydride onto the side chains of PDLLA via melt‐free radical polymerization using benzoyl peroxide as initiator. BDA was then grafted via an N‐acylation reaction. The degradation behavior of these graft copolymers could be controlled by the content of BDA. Grafting of BDA onto PDLLA reduced or neutralized the acidity of PDLLA degradation products due to dangling amine component. Also a uniform degradation of these copolymers was observed in comparison with an acidity‐induced auto‐accelerating degradation featured by PDLLA [167].
New amphiphilic graft copolymers of hyaluronic acid (HA) were prepared by grafting both hydrophobic (PLA) and hydrophilic branches (PEG) on the PLA backbone. The copolymers (PLA‐g‐HA‐g‐PEG) were characterized by spectroscopic techniques. Branched PLA with various lengths of graft chains were synthesized by ROP of L‐ or D‐lactide with polyglycidol as an initiator [168]. The branched PLLA revealed a lower T g, T m, crystallinity, and Young’s modulus and higher strain at break than the corresponding linear PLLA or PDLA film.
The PLA surface was chemically modified by a single‐step, nondestructive grafting technique using vinyl monomers such as acrylamide, maleic anhydride, and N‐vinylpyrrolidone in the vapor phase. Benzophenone was used as a photo‐initiator under solvent‐free conditions. The modified surfaces exhibit higher wettability, and the grafting was verified by X‐ray photoelectron spectroscopy, attenuated total reflection, FTIR, contact‐angle measurements, and scanning electron microscopy. The graft chain pendant groups remain functional and can subsequently be modified so that a tailor‐made surface with desired properties may be achieved [169].
Acrylic‐acid‐grafted PLA (PLA‐g‐AA) and multi‐hydroxyl‐functionalized multiwalled carbon nanotubes are melt blended to improve thermal stability and mechanical properties of the composite. The formation of a covalent bond (ester linkage) resulted in a significant improvement in compatibility [170]. Alternatively, carboxylic acid‐functionalized multiwalled carbon nanotubes were grafted onto PLLA by a one‐step in situ polycondensation reaction [171]. Acrylic‐acid‐grafted PLA, titanium tetraisopropylate, and starch blends were prepared by an in‐situ sol–gel and melt blending processes. The carboxylic acid groups of acrylic acid act as a coordination site for the titania phase to form a Ti—O—C chemical bond. This resulted in a nano‐scale dispersion of TiO2 in the polymer matrix [172].
PLA‐g‐dextran having various lengths and number of grafted chains and sugar units were synthesized using the trimethylsilyl protection method. The surface of these films is believed to be covered with hydrophilic dextran segments, which led to the suppression of cell attachment and protein absorption onto the film [173–175]. In another study, PLA‐g‐dextran copolymers were synthesized by a three‐step process: partial silylation of the dextran hydroxyl groups, ROP of DLA initiated by the remaining hydroxyl groups of dextran, followed by silyl ether deprotection under mild conditions. The emulsifying properties of these glycopolymers depend on the PLA/dextran ratio [176]. PLA‐g‐dextran and PLA‐g‐silylated dextran adopt a core–shell conformation in various solvents [177]. Studies on encapsulation and release behavior of bovine serum albumin from PLA‐g‐dextran revealed a higher loading than in PLLA microspheres [178].
Studies on gelatin‐g‐PLA were extensively reported in the literature. These degradable, in general, amphiphilic polymers are useful for parenteral drug delivery systems and tissue engineering. These copolymers were prepared by the ROP of LLA onto functionalized gelatin using bulk copolymerization at 140°C or solution copolymerization at 80°C with Sn(Oct)2 as the catalyst. The number of grafting sites on the gelatin chain could be adjusted by partial trimethyl silylation of pendant hydroxyl, amino, and carboxylic acid groups [179].
Novel triblock copolymer PLGA‐PEG‐PLGA showed a pH‐dependent hydrolytic degradation with itaconic acid (ITA), obtained from renewable resources, delivers a reactive double bond and carboxylic functional group to the end of PLGA‐PEG‐PLGA. The so obtained carboxylic groups containing copolymer (ITA/PLGA‐PEG‐PLGA was found to be more susceptible to hydrolytic degradation than the unmodified copolymer as reflected with nearly 45% decrease in M n value (in initial 10 days) when kept at pH 7.4 [180].
PLA lacks reactive functional groups and the presence of the polyester backbone limits further modification to alter its chemical and physical properties and advocate its applicability to vast domain. To overcome this limitation, PLA bearing functional side chains such as alkenes, alkynes, hydroxyl, amino, carboxylic acid, thiol, and azido groups have been prepared [105,181–185]. Among these, azide or alkyne groups are valuable addition in its structure as it allows a facile coupling azide–alkyne [3 + 2] cycloaddition “click” chemistry under mild conditions. For example, pendant azide groups in PLA were reduced to amine to assist further modification to quaternary ammonium groups using copper‐catalyzed [3 + 2] cycloaddition reaction. The resultant polymer showed an enhanced antimicrobial activity both in suspension and as a film [186]. Amphiphilic brush‐grafted copolymers of PLA‐g‐POEGMA [POEGMA, poly[(oligoethylene glycol) methacrylate] revealed a molecular architecture upon assembly, which increase their potential as drug delivery carriers. The copolymer was prepared by ATRP of oligo(ethylene glycol) methacrylate (OEGMA) macromer using brominated PLA (Br‐PLA) as a macroinitiator [187].
4.4.2 Star‐Shaped Copolymers
A block copolyester formed by the condensation reaction of PLA with hydroxyl‐terminated four‐armed PCL macroinitiators are shown in Figure 4.17. This reaction was catalyzed by two different catalysts, Sn(Oct)2 and Fe(OAc)2. The so‐formed block copolyester poly(ε‐caprolactone‐b‐lactic acid) and its blend with poly(lactic acid) was explored for adhesive application [56]. Further crosslinking reaction of thus‐obtained four‐armed polymer with diisocyanate resulted in a biodegradable polymeric material composed of well‐defined alternating hard and soft domains [188].
Precision synthesis of microstructures in star‐shaped copolymers of CL, LLA, and DXO was accomplished using a spirocyclic tin initiator and Sn(Oct)2 (cocatalyst) together with pentaerythritol ethoxylate (co‐initiator) [189]. Four‐arm star‐shaped DLLA oligomers of controlled molar mass and low dispersity were synthesized by using ethoxylated pentaerythritol initiator. The terminal hydroxyl group was converted to methacrylate (methacrylic anhydride) or 2‐isocyanatoethyl methacrylate. Photo‐crosslinking of these functional oligomers yielded networks with high gel contents. The T g of the copolymers depended on the prepolymer molar mass [190].
FIGURE 4.17 Hydroxy end‐functionalized star‐shaped PCL macroinitiators [56].
Star‐shaped PEO–PLA showed a shorter degradation times in comparison to previously reported linear PLA and PLA‐b‐PEG copolymers, along with exceptional amphiphilic characteristics, which may be appealing for their utility as excellent candidates for drug release intracellular carriers [191]. The four‐arm star‐branched block copolymer of LA and EO was investigated for the release of anticancer drugs 5‐FU and paclitaxel. The drug release of paclitaxel from the micellar nanoparticles could be better controlled, as compared with linear block copolymers. The cumulative drug release reaches 60 and 85% by 4th and 14th day, respectively [192]. A rapid and complete release of drug was due to the rapid degradation of micelles from the star‐shaped copolymer, compared to the linear block copolymers. PEGylated copolymers with CL, VL, and LA were amphiphilic in nature and formed micelles with low critical micellar concentration (CMC) values