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Poly(lactide) Stereocomplexes: Formation, Structure,

Properties, Degradation, and Applications

Hideto Tsuji

Department of Ecological Engineering, Faculty of Engineering, Toyohashi University of Technology, Tempaku-cho,Toyohashi, Aichi 441-8580, JapanE-mail: [email protected]

Received: March 23, 2005; Revised: May 18, 2005; Accepted: May 20, 2005; DOI: 10.1002/mabi.200500062

Keywords: association; biodegradable; biomaterials; blends; polyesters; stereospecific polymers

1. Introduction

When the interaction between polymers having different

tacticities or configurations prevails over that one between

polymers with the same tacticity or configuration, a stere-

oselective association of the former polymer pair takes

place. Such association is described as stereocomplexation

or stereocomplex formation. A well known and typical

example of stereocomplexation is the one between isotactic

and syndiotactic poly(methyl methacrylate) (PMMA),

which was first reported by Fox et al. in 1958.[1] The first

example of stereocomplexation (stereoselective associa-

tion) for enantiomeric polymers, i.e. between R- and

S-configured (or L- and D-configured) polymer chains, was

reported by Pauling and Corey for a polypeptide in 1953.[2]

However, it seems that the detailed structures of the

polypeptide and its assemblies are unclear. With respect to

optically active polyesters, Grenier and Prud’homme[3]

Summary: Poly(lactide)s [i.e. poly(lactic acid) (PLA)] andlactide copolymers are biodegradable, compostable, produ-cible from renewable resources, and nontoxic to the humanbody and the environment. They have been used as bio-medical materials for tissue regeneration, matrices for drugdelivery systems, and alternatives for commercial polymericmaterials to reduce the impact on the environment. Sincestereocomplexation or stereocomplex formation betweenenantiomeric PLA, poly(L-lactide) [i.e. poly(L-lactic acid)(PLLA)] andpoly(D-lactide) [i.e. poly(D-lactic acid) (PDLA)]was reported in 1987, numerous studies have been carried outwith respect to the formation, structure, properties, degrada-tion, and applications of the PLA stereocomplexes. Stereo-complexation enhances the mechanical properties, thethermal-resistance, and the hydrolysis-resistance of PLA-based materials. These improvements arise from a peculiarly

strong interaction between L-lactyl unit sequences andD-lactyl unit sequences, and stereocomplexation opens anew way for the preparation of biomaterials such ashydrogels and particles for drug delivery systems. It wasrevealed that the crucial parameters affecting stereocom-plexation are the mixing ratio and the molecular weight ofL-lactyl and D-lactyl unit sequences. On the other hand,PDLAwas found to form a stereocomplex with L-configuredpolypeptides in 2001. This kind of stereocomplexation iscalled ‘‘hetero-stereocomplexation’’ and differentiated from‘‘homo-stereocomplexation’’ between L-lactyl and D-lactylunit sequences. This paper reviews the methods for tracingPLA stereocomplexation, the methods for inducing PLAstereocompelxation, the parameters affecting PLA stereo-complexation, and the structure, properties, degradation, andapplications of a variety of stereocomplexed PLA materials.

Macromol. Biosci. 2005, 5, 569–597 DOI: 10.1002/mabi.200500062 � 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Review 569

found stereocomplexation between enantiomeric poly(a-methyl-a-ethyl-b-propiolactone) (PMEPL), R- and

S-PMEPL, in 1984. Later, Ikada et al. reported stereo-

complexation between enantiomeric polylactide [i.e. poly-

(lactic acid) (PLA)], poly(L-lactide) [i.e. poly(L-lactic acid)

(PLLA)] and poly(D-lactide) [i.e. poly(D-lactic acid)

(PDLA)] in 1987.[4] Although these polyesters, PMEPL

and PLA, are a-substituted, Voyer and Prud’homme

reported stereocomplexation between b-substituted poly-

esters, poly(b-proriolactone)s, having different side groups(1,1-dichloroethyl or 1,1-dichloropropyl).[5] The typical

polymers having stereocomplexationability are summar-

ized in Table 1.[6] Stereocomplexation can occur between

isotactic and syndiotactic polymers or R- and S-configured

polymers having different chemical structures. The

reported examples are stereocomplexation between iso-

tactic PMMA and syndiotactic poly(methacrylic acid),[7]

between isotactic PMMA and syndiotactic poly(isobutyl

methacrylate),[8] and between PDLA and L-configured pep-

tides.[9] Slager and Domb described such kinds of stereo-

complexation between polymers with different chemical

structures as ‘‘hetero-stereocomplexation’’ and discri-

minated it from stereocomplexation between polymers

having identical chemical structures (‘‘homo-stereocom-

plexation’’).[9]

Stereocomplexation between PLLA and PDLA can

occur in solution, in a solid (bulk) state from the melt,

during polymerization, or during hydrolytic degradation, as

long as L-lactide (or L-lactyl) unit sequences and D-lactide

(or D-lactyl) unit sequences coexist in a system.[6] In other

words, PLA stereocomplexation can take place both in

enantiomeric PLA-based polymer blends and in non-

blended stereoblock PLA. Here, lactyl unit means a half

lactide unit. The synthetic procedures and structures of

PLLA, PDLA, and stereoblock PLA are given in Figure 1.

Stannous octoate (stannous 2-ethylhexanoate) and lauryl

alcohol (1-dodecanol) have been used frequently as initiator

and coinitiator, respectively, for the synthesis of PLA

homopolymers. These synthetic routes in the presence of

comonomers can be utilized to prepare copolymers having

L- or D-lactyl units.

When L-chains and/or D-chains are present in a system,

various types of crystallites can be formed (Figure 2).[19]

Figure 2 parts (a) and (b) show crystallites composed solely

of L-chains and D-chains, respectively. We call such

crystallites ‘‘homo-crystallites’’ and the formation of

homo-crystallites ‘‘homo-crystallization’’. In this case,

either L- or D-chains, not both, are present in the system.

However, when both L-chains and D-chains are present in a

system, three types of crystallites, Figure 2 parts (c)–(e),

can be formed. Figure 2(c) represents stereocomplex cry-

stallites (or racemic crystallites), where L-chains and

D-chains have a peculiarly strong interaction compared

with that between identical configurations and, therefore,

L- and D-chains are packed side by side. It should be noted

that the actual shape of the unit lattice of the PLA

stereocomplex showing in Figure 5 is different from that

showing in Figure 2(c).When an interaction between chains

having identical configurations prevails against that one

between polymers with different configurations, L-chains

and D-chains assemble separately to form homo-crystal-

lites, as illustrated in Figure 2(e). The formation of

crystallites where L- and D-chains are packed randomly, as

given in Figure 2(d), has not been reported so far. Such non-

selective packing is expected to occur when interactions

between chains with the same and different configurations

are identical. In the case of PLA, when L- and D-chains are

mixed non-equimolarly or when L- and D-chains have

relatively highmolecularweights, homo-crystallites aswell

as stereocomplex crystallites are formed.[6,20–24]

Stereocomplexation of PLA is composed solely of a

stereocomplex crystallization (racemic crystallization)

process, in marked contrast to stereocomplexation between

isotactic and syndiotactic PMMA, where an association

Hideto Tsuji is an Associate Professor at the Faculty of Engineering, Toyohashi University ofTechnology (Aichi, Japan). He was born in Osaka (Japan) in 1961. He received his Ph.D. degree inpolymer chemistry in 1992 from the Kyoto University (Japan) under the supervision of ProfessorYoshito Ikada. His Ph.D. work focused on the stereocomplexation between enantiomeric poly(lacticacid)s. After he finished his Ph.D. program, he moved to the Technology Development Center,Toyohashi University of Technology as a Research Associate in 1990. In 1996 as a Visiting Researcher,he joined the group of Professor William Bonfield and Dr. Raymond Smith at the Queen Mary andWestfield College, University of London (U.K.), where he studied the preparation methods ofbiodegradable porous materials. He became an Associate Professor at the Faculty of Engineering,Toyohashi University of Technology, in 1997. His research interests include the developments ofpoly(lactide)s and other biodegradable polyesters for a variety of applications and the manipulation oftheir physical properties and degradability. He has been investigating the synthesis, treatments, blend-ing, physical properties, crystallization, hydrolytic degradation, biodegradation, thermal degradation,and recycling of poly(lactide)s and other biodegradable polyesters. He has authored and coauthoredmore than 75 original research papers, 15 review articles, 5 patent articles, and 25 book chaptersincluding Chapter 5 in ‘‘Polyesters III (Biopolymers, vol. 4, Wiley-VCH, 2002)’’.

570 H. Tsuji

Macromol. Biosci. 2005, 5, 569–597 www.mbs-journal.de � 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Table 1. Stereocomplexationable polymers.[6]

Isomeric type Polymer type Polymer Reference

Syndiotactic and isotactic Vinyl polymer Poly(methyl methacrylate) (PMMA) Fox et al.[1]

Isotactic R- and S- (or L- and D-) Polyether Poly(tert-butylethylene oxide) Sakakihara et al.[10]

(chiral center in the main chain) Poly(epichlorohydrin) Signfield and Brown[11]

Polythioether Poly(tert-butylethylne sulfide) Dumas et al.[12]

Polyketone Poly(propylene-carbon monoxide) Jiang et al.[13]

Poly(1-butene-carbon monoxide) Jiang et al.[13]

Poly(allylbenzene-carbon monoxide) Jiang et al.[13]

Polyamide (Polypeptidic) Poly(g-methyl glutamate) Yoshida et al.[14]

Poly(g-benzyl glutamate) Tsuboi et al.[15]

Polyamide (Non-polypeptidic) Poly(hexamethylene-2,3-di-O-methyl-L-tartaramide)

Iribarren et al.[16]

Polyester Poly(a-methyl-a-ethyl-b-propiolactone) (PMEPL)

Grenier and Prud’homme[3]

Poly[b-(1,1-dichloroethyl)-b-propiolactone]

Voyer and Prud’homme[5]

Poly[b-(1,1-dichloropropyl)-b-propiolactone]

Voyer and Prud’homme[5]

Polylactide, polyl(lactic acid) (PLA) Ikada et al.[4]

Isotactic R- and S- (or L- and D-) Vinyl polymer Poly(g-methylbenzyl methacrylate) Hatada et al.[17]

(chiral center in the side chain) Poly(N-methacryloyl-L-leucinemethyl ester)

Sanda et al.[18]

Figure 1. Synthesis andmolecular structures of PLLA [(a) and (b)], PDLA [(c) and (d)], and stereo-block isotactic PLA[(e) and (f)].

Poly(lactide) Stereocomplexes: Formation, Structure, Properties, Degradation, and Applications 571


process of isotactic and syndiotactic PMMA is followed by

crystallization of the associated PMMA chain pairs.[25]

Most of the reported stereocomplexation between enantio-

meric polyesters are expected to proceed via the same

process as that for PLA stereocomplexation, i.e., a stereo-

complex crystallization process. With respect to PLA-

based stereocomplexation, the ratio of stereocomplex

crystallites to homo-crystallites is affected by numerous

parameters, such as the molecular weights and optical

purities of the polymers and themixing ratio of the isomeric

chains, as elucidated by intensive studies.[6,20–24,26–29]

Those parameters expected to affect PLA-based stereo-

complexation are listed in Table 2 and detailed information

is given below.

Since PLA and lactide copolymers are biodegradable,

compostable, producible from renewable resources, and

nontoxic to the human body and the environment, they have

been used as biomedical materials for tissue regeneration,

matrices for drug delivery systems, and alternatives for

commercial polymericmaterials to reduce the impact on the

environment.[30–37] PLA stereocomplexation due to the pe-

culiarly strong interaction between L-lactyl unit sequences

and D-lactyl unit sequences is expected to improve a

variety of properties of PLA-based materials and open

novel methods to prepare such materials. Although

numerous reviews or feature articles with respect to PLA

have been published, the PLA-based stereocomplex is

described only in parts of these articles,[9,30–37] excluding a

short feature article published in 2000.[6] This paper

reviews the methods for tracing PLA stereocomplexation,

the methods for inducing PLA stereocompelxation, the

parameters affecting PLA stereocomplexation, and the

structure, properties, degradation, and applications of a

variety of stereocomplexed PLA materials.

2.Methods forTracingPLAStereocomplexation

Numerous methods have been reported for tracing PLA

stereocomplexation. The representative methods are des-

cribed in this section and such information is required to

understand the subsequent sections.

2.1. Differential Scanning Calorimetry (DSC)

DSC is one of the most effective and simple methods for

monitoring PLA stereocomplexation. Figure 3 gives typical

DSC curves for the blends of PLLA and PDLAwith diffe-

rent mixing ratio (XD) values.[21] XD is defined as follows:

XD ¼ Weight of PDLA=Weight of PLLA and PDLA

ð1Þ

The specimens were prepared by precipitation of a

methylene chloridemixed solution of PLLA andPDLA into

stirred methanol. The peak at around 180 8C for PLLA or

PDLA (XD¼ 0 or 1) is ascribed to the melting of PLLA or

PDLA homo-crystallites, while a new melting peak at

around 230 8C appears in the blend specimens. The new

peak is attributed to the melting of stereocomplex crystal-

lites. A similar increase in melting temperature (Tm)

upon stereocomplexation was reported by Grenier and

Prud’homme for blends between R- and S-PMEPL.[3] The

enthalpyofmelting(DHm)ofstereocomplexcrystallitesgives

a maximum at mixing ratio XD of 0.5 and with a deviation of

XD from 0.5 the DHm of homocrystallites increases. This

reflects the fact that equimolar mixing is favored for

stereocomplexation.

Tsuji and Ikada have estimated the equilibrium melting

temperature (Tm0 ) of PLA stereocomplex crystallites by

extrapolation of Tm0 values for different optical purities,

which were obtained by the Hoffman-Weeks procedure

using experimental Tm values, to 100% optical purity.[23]

The estimated Tm0 value of 279 8C is much higher than the

205 8C (Tsuji and Ikada[38,39]), 212 8C (Tsuji and Ikada[40]),

and 215 8C (Kalbs and Pennings[41]) reported for homo-

crystallites of PLLA. The reported DHm values for the

crystals having an infinite thickness [DHm(100%)] for PLA

Figure 2. Crystallite models for enantiomeric L- and D-poly-mers.[19] (a) a homo-crystallite composed of L-polymer chains; (b)a homo-crystallite composed of D-polymer chains; (c) a stereo-complex (racemic) crystallite where L- and D-polymers are packedside by side; (d) a crystallite where L- and D-polymer chains arepacked randomly; (e) a mixture of (a) and (b).

572 H. Tsuji


stereocomplex, 142 J g�1 (Loomis et al.[42]) and 146 J g�1

(Tsuji et al.[43]) are in the range of DHm(100%) values for

homo-crystallites, 93 J g�1 (Fischer et al.[44]), 135 J g�1

(Miyata and Masuko[45]), 142 J g�1 (Loomis et al.[42]), and

203 J g�1 (Jamshidi et al.[46]). In our case, the DHm(100%)

for the PLA stereocomplex was calculated from the

experimental DHm value (102 J g�1) and the crystallinity

(Xc) value (70%) obtained with wide-angle X-ray scatter-

ing,[43] whereas the procedure for the calculation of

DHm(100%) for the PLA stereocomplex was not given in

the literature.[42] The physical properties, including the

detailed thermal properties of stereocomplexed PLA and

nonblended PLLA in comparison with other biodegradable

polyesters, are summarized in Table 3.[36]

2.2. Wide-Angle X-Ray Scattering (WAXS)and Small-Angle X-Ray Scattering (SAXS)

In the first report on PLA stereocomplexation, the WAXS

profiles of blends having different XD values are shown

(Figure 4) and in the same report DSC thermograms are

presented. Themain peaks of PDLA (XD¼ 1) film appear at

Table 2. The parameters affecting PLA stereocomplexation.

Molecular Structures Molecular Characteristics Procedures Parameters

1. PLLA/PDLA 1. Overall molecular weight 1. Bulk 1. Mixing ratio of polymers(for polymer blending)

2. L-lactide copolymer/D-lactide copolymer

2. Averaged sequence lengths(molecular weights) of L- andD-lactide (lactic acid) units(for linear copolymers).

1.1. Crystallization at a fixedtemperature from the meltor after melt-quenching

2. Melting temperature and time3. Crystallization or polymerization

temperature and time (1.1 and 1.3)4. Cooling rate from the melt (1.2.)or heating after melt-quenching

3. PLLA-b-PDLA 3. Kinds and averagesequence lengths(molecular weights)of comonomer units(for copolymers).

1.2. Cooling from the melt orheating after melt-quenching

4. Degree of substitution ornumber of graft chain perunit length of main chain(for graft copolymers)

1.3. During polymerization

2. Solution casting 1. Mixing ratio of polymers(for polymer blending)

2. Kind of solvent3. Temperature and time for solventevaporation

3. Precipitation 1. Mixing ratio of polymers(for polymer blending)

3.1. Precipitation or gel formation ata constant polymerconcentration

3.2. Precipitation into non-solvent

2. Kinds of solvent and precipitant3. Precipitation temperature4. Share rate (Stirring rate) of solventor precipitant during precipitation

4. Stepwise assembly in solution 1. Solution concentration andtemperature

2. Immersion time (for oneimmersion) and number of times

5. Drawing or orientation(after preparation by theprocedures 1–3)

1. Drawing method (Uniaxialor Biaxial)

2. Step number of drawing(One, two, or more)

3. Drawing temperature andannealing time

6. Compression (after preparationof monolayer film)

1. Compression temperatureand pressure



2y values of 15, 17, and 198,[4] which are comparable with

the results for the a form of PLLA crystallized in a pseudo-

orthorhombic unit cell of dimensions: a¼ 1.07 nm,

b¼ 0.595 nm, and c¼ 2.78 nm, which contains two 103helices.[36,47] The most intense peaks of equimolarly

blended film (XD¼ 0.5) are observed at 2y values of 12,

21, and 248. These peaks are for the PLA stereocomplex[4]

crystallized in a triclinic unit cell of dimensions: a¼0.916 nm, b¼ 0.916 nm, c¼ 0.870 nm, a¼ 109.28,b¼ 109.28, and g¼ 109.88, in which L-lactide and D-lactide

segments are packed parallel taking 31 helical conforma-

tion.[47] The crystal structure of the PLA stereocomplex

proposed by Okihara et al.[47] is demonstrated in Figure 5.

The lattice containing a PLLA or PDLA chain with a 31helical conformationhas the shape of an equilateral triangle,

which is expected to form equilateral-triangle-shaped

single crystals of the PLA stereocomplex.[48] On the other

hand, Okihara et al. found that in the X-ray and electron

diffraction patterns of drawn fibers of the PLA stereo-

complex, the equatorial reflections were sharp, but those on

the layer lines were largely broadened in the direction

parallel to the layer line, becomingmore diffuse as the layer

order increases. On the basis of the paracrystalline theory,

they estimated the degree of shift disorder among polymer

chains in the direction parallel to the molecular axis to be

0.1.[49] Furthermore, Brizzolara et al.[50] compared the

WAXS profiles from actual stereocomplexed specimens

and a Force-Field simulated stereocomplex. They also

proposed the growth mechanism of the stereocomplex

equilateral-triangle-shaped single crystal.

Figure 3. DSC thermograms of PLLA/PDLA blends withdifferent XD values.[21] Viscosity-average molecular weights(Mvs) of PLLA and PLLA are both 3.6� 105 g �mol�1.

Table 3. Physical properties of stereocomplexed PLA and some biodegradable polyesters.[36]

Physical properties Stereo-complexed

PLA

PLLA PDLLA SyndiotacticPLA

PCL Poly[(R)-3-hydroxybutyrate]

(R-PHB)

Poly(glycolide)(PGA)

Tm(8C) 220–230 170–190 – 151 60 180 225–230Tm0(8C) 279 205, 212, 215 – – 71, 79 188, 197 –

Tg(8C) 65–72 50–65 50–60 34 �60 5 40DHm(100%)a) (J g�1) 142, 146 93, 135, 142,

203– – 142 146 180–207

DEtdb) (kJ �mol�1) 205–297 87–104 – – – – –

Density (g � cm�3) – 1.25–1.29 1.27 – 1.06–1.13 1.177–1.260 1.50–1.69Solubility parameter (dp) (25 8C) (J

0.5 � cm�1.5) – 19–20.5,22.7

21.1 – 20.8 20.6 –

[a]58925 in chloroform(deg � dm�1 � g�1 � cm3) – �155� 1 0 – 0 þ44c) –

WVTRd) (g �m�2 � d�1) – 82–172 – – 177 13e) –Tensile strength (GPa) 0.88f) 0.12–2.3f) 0.04–0.05g) – 0.1–0.8f) 0.18–0.20f) 0.08–1f)

Young’s modulus (GPa) 8.6f) 7–10f) 1.5–1.9g) – – 5–6f) 4–14f)

Elongation at break (%) 30f) 12–26f) 5–10g) – 20–120f) 50–70f) 30–40f)

a) Enthalpy of melting of crystal having infinite size.b) Activation energy for thermal degradation estimated by thermogravimetry at a constant temperature (250–270 8C).c) 300 nm, 23 8C.d) Water vapor transmission rate at 25 8C.e) Poly[(R)-3-hydroxybutyrate-co-3-hydroxyvalerate] (94/6).f) Oriented fiber.g) Non-oriented films.

574 H. Tsuji


The result obtained from SAXS analysis was solely for

the long period of the PLA stereocomplex precipitated from

acetonitrile solutions at 80 8C and annealed at 216 8C.[43]

The estimated long period was 12 nm, which is much

smaller than the 22–35 nm reported for PLLA films

crystallized at 120–160 8C from the melt.[51] Using the

crystallinity (Xc) value obtained by a WAXS profile (70%),

the estimated thickness values of stereocomplex crystalline

and amorphous regions were 8.4 and 3.6 nm, respec-

tively.[43] The estimated thickness of stereocomplex crys-

talline regions is also much smaller than the 13–22 nm

reported for PLLAfilms crystallized at 120–160 8C.[51] The

differences in long period and crystalline thickness between

the stereocomplex and PLLA are partly ascribed to the

differences in the specimen preparation method and

conditions.

2.3. Infrared (IR) and Raman Spectroscopy

Kister et al.[52] observed IR and Raman spectral changes in

peak shapes and wavelengths upon PLA stereocomplex-

ation. Later, by the use of FT-IR, Zhang et al.[53,54] found

that a very small low-frequency shift (about 1 cm�1) of

nas(CH3) and a larger low-frequency shift (about 5 cm�1) of

n(C O) were observed during stereocomplex crystalliza-

tion from the melt (Figure 6). The low-frequency shifts of

the stretching vibration modes of the methyl and carbonyl

groups confirmed for the first time that the interaction

between the chains in the PLA stereocomplex is ascribed to

the CH3��O C hydrogen bonding. Another interesting

result is that the peak shift of the n(C O) band already

occurs in the induction period, which indicates that the

CH3��O C interaction is the driving force for the racemic

nucleation of the PLA stereocomplex.[53,54] Moreover, 2D

correlation analysis indicates that the structural adjustment

of the CH3 group occurs prior to that of the C–O–C

backbone during the stereocomplexation process. Although

van derWaals interaction between the hydrogen of CH3 and

the oxygen of O C has been suggested by Brizzolara

et al.,[50] Zhang et al. indicated for the first time that the

hydrogen bonding is the driving force for the nucleation of

PLA stereocomplex crystallites.[53,54]

Figure 4. WAXS profiles of PLLA/PDLA blends havingdifferent XD values.[4] Solid line, dashed line, and dashed/singledotted line are for XD¼ 0.5, 0.75, and 1, respectively.

Figure 5. Crystal structure of PLA stereocomplex.[47] The lines between PLLA and PDLAchains were added to original figure.



2.4. 1H and 13C NMR Spectroscopy

Tsuji et al. estimated the degree of PLA stereocomplexation

in a concentrated solution of equimolar PLLA and PDLA

by theuseof 1HNMRspectroscopy, as shown inFigure7.[26]

Broad peaks in addition to sharp peaks appeared in the

resonance lines of the methine and methyl groups and the

areas of the broad peaks increased with time. These broad

peaks are ascribed to the chains adjacent to stereocomplex

micro-crystallites, i.e. folding chains and tie chains. The

total peak area decreased because the PLA chains in the

stereocomplex crystallites gave no peaks. The shoulder

which appeared in the resonance line of CHCl3 may be due

to the CHCl3 surrounding the folding and tie chains. The

decrease in the peak areas of themethine andmethyl groups

continued for more than fifty days and the peak areas

decreased below 50%of the initial values. Such phenomena

reflect the formation of stereocomplex crystallites in

concentrated solutions and the increase in number and/or

thickness of the stereocomplex crystalline regions.

Figure 6. Temporal changes of the IR spectra in the C–H stretching region ofmethyl group(a) and C O stretching region (b) during the melt-crystallization process of PLLA/PDLAstereocomplex at 220 8C, respectively.[54]

Figure 7. 400 MHz 1H NMR spectra of equimolarly mixed chloroform solution of PLLAand PDLA at 17.5 g � dL�1 and 25 8C.[26]

576 H. Tsuji


13C NMR spectroscopy is also an effective method for

tracing PLA stereocomplexation.[43] Figure 8 gives high-

resolution solid-state CP/MAS 13C NMR spectra of PLA

stereocomplex precipitates and nonblended PDLA pre-

cipitates, and an as-cast amorphous poly(D,L-lactide)

(PDLLA)film, togetherwith a 13CNMRspectrumofPDLA

in CDCl3. Upon stereocomplexation, a new peak appeared

at 173.3 ppm (Peak I) for carbonyl carbon, whereas explicit

new peaks were not observed for the methine and methyl

carbons. Later, a similar spectral change upon stereocom-

plexation was monitored for carbonyl carbon by Kister

et al.[52]

We performed a component analysis solely for carbonyl

carbon because of the appearance of the new peak due

to stereocomplexation. Figure 9 illustrates the component

analysis for the total 13CNMR spectrum of carbonyl carbon

in the stereocomplex precipitates, and the 13C chemical

shifts and spin-lattice relaxation times (T1C) of components

A–D in resonance lines I–III are described in the caption of

Figure 9. The assignments of components A–D in the

reported article are as follows.[43] Component A in line III is

ascribed to PLA chains in the amorphous regions because

the chemical shift of line III is very close to those of the

amorphous PDLLAfilm and the PDLA in solution, and also

because of its very short T1C value (5.4 s). Components C

and D in line I are assignable to the PLA chains in the

stereocomplex crystalline regions because line I is not

observed for the crystallized nonblended PDLA and PLLA

precipitates or for the amorphous PDLLA film. Relatively

high and low T1C values of components C and D, 128 and

17 s, suggest that the chains of these components are in a

rigid and disordered state, respectively. Component B

corresponds to line IIwhichmay be ascribed to the chains in

the homo-crystalline regions, because the T1C value is

rather high (40 s) and has a very similar chemical shift to

that of the precipitates of the nonblended PDLA or PLLA.

2.5. Light Scattering (LS) Measurements

The aggregation behavior of isotactic and syndiotactic

PMMAwas monitored by Vorenkamp and Challa using the

LS method.[55] They demonstrated that the aggregation of

isotactic and syndiotactic PMMA caused no change in the

radius of gyration (ca. 30 nm) but an increase in molecular

weight. For stereocomplexation of PLA homopolymers,

PLLA and PDLA, the LS method has not been applied, but

Portinha et al.[56,57] observed aggregation behavior in

nonblended and blended solutions of poly(L-lactide)-block-

poly(e-caprolactone) (PLLA-b-PCL) and poly(D-lactide)-

block-poly(e-caprolactone) (PDLA-b-PCL). They revealedthat the hydrodynamic radii of assemblies in the enantio-

meric blended solution, 200 nm, were higher than those of

nonblended polymer solutions and that the radius distribu-

tion in the enantiomeric blended solution was sharper than

that in nonblended polymer solutions.

2.6. Viscometry

In concentrated solutions, the formed PLA stereocomplex

crystallites acted as physical crosslinks. The crosslinks

raise the solution viscosity and finally cause gel forma-

tion.[26] Figure 10 depicts the time change of the relative

viscosity of a mixed chloroform solution of equimolar

PLLA and PDLA with different concentrations. The

increase in viscosity occurs at concentrations exceeding a

critical level. In Figure 10, the critical concentration is in the

Figure 8. 50 MHz CP/MAS 13C NMR spectra of different PLAspecimens at 40 8C:[43] (A) PDLA precipitates; (B) stereocom-plex precipitates; (C) PDLLA film; (D) 13C NMR spectrum ofPDLA in chloroform-d.

Figure 9. Component analysis for the total 13C NMR spectrumof carbonyl carbon in the stereocomplex precipitate:[43] (A)noncrystalline (amorphous) component (169.7 ppm, T1C¼ 5.4 s);(B) homo-crystalline component (172.0 ppm, T1C¼ 40 s); (C)rigid stereocomplex crystalline component (173.3 ppm, T1C¼128 s); (D) disordered sterocomplex crystalline component(173.3 ppm, T1C¼ 17 s).



range of 10–12.5 g � dL�1 and this value depends onvarious

parameters such as the molecular weight, mixing ratio of

PLLA and PDLA, and solution temperature, as mentioned

below.

2.7. Rheological Measurements

Similar to theviscosity, the storagemodulus (G0) of the PLAsolution is increased by stereocomplexation due to the

reason given by Tsuji et al.[26] The dried specimen obtained

by solvent evaporation of a PLA stereocomplex gel has

higherG0 values for a wide temperature range.[24] Figure 11

gives the G0 of a nonblended PLLA film (XD¼ 0), and

blended films of PLLA/PDLA¼ 3/1 (XD¼ 0.25) and 1/1

(XD¼ 0.5), respectively. Because of its high brittleness

arising from a low molecular weight, measurements for

nonblended PLLA film could not be carried out for tem-

peratures exceeding 100 8C. The loss tangent (tan d) peaksat around 60 8C for all films and at around 180 8C for the 3/1

blended film are attributed to the glass transition and

melting of homo-crystallites. The G0 of all films decreased

above the glass transition temperature (Tg) and that of the 3/

1 blended film became lower above the Tm of the homo-

crystallites. Although the 1/1 blended film having solely

stereocomplex crystallites gradually decreased with tem-

perature above Tg, it retained the highestG0 among the films

from room temperature to Tm of stereocomplex (ca.

220 8C). Even 3/1 film having homo-crystalline regions as

well as the stereocomplex crystalline regions maintained

non-zero G0 values for temperatures up to 220 8C, meaning

that the presence of stereocomplex crystallites enhanced the

heat-resistance of PLA-based materials for temperatures

above Tg.

2.8. Tensile Properties

Stereocomplexation improves the tensile properties of

PLA-based materials.[24] Figure 12 shows the tensile

properties of nonblended PLLA or PDLA films and their

equimolarly (XD¼ 0.5) blended films. At the weight-

average molecular weight (Mw) of 1� 105–1� 106 g �mol�1, the blended film surpassed the nonblended films in

all the tensile properties (tensile strength, Young’smodulus,

and elongation at break). The main reason for the increased

tensile properties of equimolarly blended films at relatively

lowMw is the formation of stereocomplexmacro-gel during

solvent evaporation, as stated in Section 2.6, whereas the

reason for those at relatively high Mw is the formation of

smaller spherulites in the blended films.

2.9. Polarization Optical Microscopy (POM)

The growth rate, induction period, and morphology of the

spherulites of stereocomplex crystallites as well as those of

homo-crystallites can be monitored by POM.[22–24,58] The

PLA spherulites containing solely stereocomplex crystal-

lites can be formed in the equimolarly blended film of

PLLA and PDLA (Figure 13).[58] The spherulitic structure

of PLA stereocomplex crystallites was different from that

of homo-crystallites with polygonal shapes, which can be

seen for nonblended PLLA or PDLA having low molecular

weights at low temperatures.[59,60] On the other hand, by

the use of POMaswell as the scanning electronmicroscopy,

the porous structure of dried stereocomplex gels can be

observed (Section 3.2.1).[24]

Figure 10. Relative viscosity of mixed chloroform solutions ofequimolar PLLA [viscosity-average molecular weight(Mv)¼ 4.2� 104 g �mol�1] and PDLA (Mv ¼ 4.5� 104 g �mol�1)with different concentrations at 25 8C.[26]

Figure 11. Storage modulus (G0) and loss tangent (tan d) for as-cast nonblended and blended films from PDLA (Mw ¼ 1.2�105 g �mol�1) and PLLA (Mw ¼ 1.0� 105 g �mol�1) with diffe-rent XD values.[24]

578 H. Tsuji


2.10. Scanning Electron Microscopy (SEM),Electron Diffraction (ED), and TransmissionElectron Microscopy (TEM)

SEM observation revealed that PLA stereocomplex parti-

culate precipitates (Figure 14) are formed in acetonitrile

solution and their size and shape depends on various para-

meters, as shown inTable 2.[27] The stereocomplex particles

were disk-shaped under the conditions of 1 g � dL�1, 80 8C,and XD¼ 0.5. Upon decreasing the temperature or increas-

ing the polymer concentration, the stereocomplex particles

becamemore spherical, whereas upon deviation ofXD from

0.5, the stereocomplex particles became equilateral-triangle-

plate-shaped. The equilateral triangular shape is very

similar to that of the PLA stereocomplex single crystals

observed by TEM [Figure 15(A)].[47] Cartier et al.[61] found

that such triangular crystals as observed for the PLA

stereocomplex can be utilized as a morphological marker

for the frustrated character of the chain packing of a

polymer in the unit cell. On the other hand, Okihara et al.[47]

demonstrated that PLA stereocomplexation can be traced

by the use of obtained ED patterns.

2.11. Atomic Force Microscopy (AFM)

Similar to the SEM and TEM observation, AFM can moni-

tor the equilateral triangle-shaped single crystal and disks

of the PLA stereocomplex (Figure 16).[9]

3. Methods for Inducing PLAStereocomplexation

PLA stereocomplexation takes place in the absence of a

solvent (in bulk: crystallization from the melt or during

polymerization), or in the presence of solvent (in solution).

As tabulated inTable 2, PLA stereocomplexation is affected

by numerous parameters. Tsuji et al.[6,20–24,26–29,36] and

Murdoch and Loomis[62–66] investigated the parameters’

effects on the stereocompelxation of PLA homopolymers

utilizing different methods under a wide variety of

conditions.

3.1. In Bulk or Solid State

3.1.1. Crystallization from the Melt

There are four representative procedures for crystallization

from the melt; (1) crystallization at a fixed temperature (Tc)

directly from the melt, (2) crystallization at a fixed Tc after

quenching from the melt, (3) crystallization during cooling

from the melt, (4) crystallization during heating of melt-

quenched specimens.[67] Procedure (1) is utilized to trace

the radius growth rate of spherulites (G) and the induction

period for spherulite formation (ti). Figure 17 illustrates the

G and ti values for spheruiltes of stereocomplex crystallites

and homo-crystallites in PLLA, PDLA, and equimolar

PLLA/PDLA blended films crystallized through Procedure

(1). The polarization optical photomicrographs are given in

Figure 13.[58] The spherulites composed of stereocomplex

crystallites have an extremely high G and a short ti com-

pared with those of the homo-crystallites of either PLLA or

PDLA, as shown in Figure 17. Such rapid formation and

growth of PLA stereocomplex crystallites were observed

even when an equimolar mixture of PLLA and PDLA both

Figure 12. Tensile properties of nonblended films and equimo-larly (XD¼ 0.5) blended film from PLLA (XD¼ 0) and PDLA(XD¼ 1) as a function ofMw.

[24]



Figure 13. Spherulites of PLLA (Mw ¼ 1.0� 104 g �mol�1) (A), PDLA (Mw ¼ 2.2�104 g �mol�1) (B), and their equimolarly blended films (C, D) crystallized at 140 8C (A–C)and 190 8C (D) from the melt at 250 8C.[58]

Figure 14. SEM photographs of PLA stereocomplex particles precipitated fromacetonitrile solutions with different concentrations.[27] (A) 0.1 g � dL�1; (B) 1 g � dL�1; (C)3 g � dL�1; (D) 10 g � dL�1.

580 H. Tsuji


with low molecular weights was quenched from the

melt.[22,62] The hydrogen bonding between methyl hydro-

gen and carbonyl oxygen as revealed by Zhang et al.[53,54] is

expected to enhance such rapid spherulite formation and

growth of PLA stereocomplex crystallites. The spherulites

of stereocomplex crystallites had normal morphology very

similar to that of homo-crystallites when only stereocom-

plex crystallites were contained in the spherulites.[22,23] In

contrast, the spherulite morphology became complicated

when both stereocomplex crystallites and homo-crystallites

were formed simultaneously in the spherulites.[22,23]

Although there has been no report with respect to Pro-

cedure (2), the quenching process should enhance stereo-

complex crystallization by increasing the spherulite nuclei,

as reported for homo-crystallization of PLLA.[67] In

Procedures (1) and (2), the stereocomplex crystallites are

predominantly formed by crystallization at Tc between the

Tm values of homo-crystallites (170–180 8C) and stereo-

complex crystallites (220–230 8C).[22,62] For Procedure

(3), Brochu et al.[68] reported the epitaxial crystallization of

homo-crystallites of PLLA on the stereocomplex crystal-

lites of PLLA and poly(L-lactide-co-D-lactide) (20/80)

when the two polymers were mixed at a ratio of 80/20

and crystallized during slow cooling at 1 or 2 8Cmin�1 from

themelt.With regard to epitaxial crystallization of aliphatic

polyesters, Soldera and Prud’homme[69] observed epitaxial

crystallization of R-configured poly(a-methy-a-propyl-b-propiolactone) (PMPPL) onto S-configured PMEPL crys-

tallites. For Procedure (4), Urayama et al.[70] found that an

aluminum complex of a phosphoric ester combined with

hydrotalcite (NA) executively enhance the nucleation of

stereocomplex crystallites, whereas talc cannot suppress

the homo-crystallization of PLLA or PDLA.

3.1.2. During Polymerization

Spinu et al.[71–73] proposed a novel method for stereo-

complexation between PLLA and PDLA; polymerization

of LLA and DLA in the presence of PDLA and PLLA,

respectively, after mixing LLA and PDLA (or DLA and

PLLA). With this method, they successfully prepared well-

stereocomplexed PLA materials. In the strict sense of the

word, this method may not be ‘‘template polymeriza-

tion’’,[74] but effectively utilizes the fact that the polymer-

ized chains have strong interaction with the template

chains.

3.1.3. Upon Compression

Bourque et al.[75] and Pelletier and Pezolet[76] reported that

stereocomplexation occurs upon the compression of the

Figure 15. TEM photographs and electron diffraction patternsof PLAstereocomplex single crystal (A) and particle (B) formed indilute acetonitrile solutions.[27]

Figure 16. AFM photographs of equilateral-triangle-shapedsingle crystal (A) and disks (B) of PLA stereocomplex (Courtesyof Prof. Domb).[9] Reprinted from Adv. Drug Delivery Rev., Vol.55, Slager and Domb, ‘‘Biopolymer Stereocomplexes’’, pp. 549–583, 2003, with permission of Elsevier.



monolayer of PLLA/PDLA mixture films. They prepared

Langmuir films of PLLA andPDLA and then observed their

structural changes by the use of surface-pressure measure-

ments and polarization modulation infrared reflecting-

absorption spectroscopy (PM-IRRAS). They indicated that

a stereocomplex bilayer in equilibrium with the monolayer

was formed at the air-water interface by compression.

3.1.4. Upon Orientation

Tsuji et al. revealed that stereocomplex cystallization of the

equimolar PLLA/PDLA fibers were enhanced by hot-

drawing to high ratios.[77] The hot-drawing process causes

expanded chains or increases the surface area per unit

molecule and, therefore, raises the probability of interaction

between PLLA and PDLA segments. This causes increased

Xc and Tm of stereocomplex crystallites and enhances

tensile properties.[62,77]

3.1.5. Upon Hydrolytic Degradaion

Li et al. found that stereocomplexation can occur in poly(L-

lactide-co-D-lactide) with a thickness of mm order after a

long-term hydrolytic degradation (25 or 30 weeks) as

mentioned in detail in Section 4.2.2.[78–82] The hydrolytic

degradation induces a decreased molecular weight, which

elevates the mobility of PLA chains in addition to the

presence of water as a plasticizer, and selective removal of

relatively atactic sequences, leaving relatively isotactic

chains. These three factors enhance PLA stereocomplexa-

tion between remaining L-lactyl unit sequences and D-

lactyl unit sequences. However, when thin specimens

(thickness< 200 mm) were used, no stereocomplexation

was observed for poly(D,L-lactide)[83] and an amorphous-

made equimolar blend of PLLA and PDLA,[84] even when

hydrolytic degradation was continued for 20–24 months.

This supports the fact that core-accelerated hydrolysis

of thick specimens should have induced PLA stereocom-

plexation.

3.2. In Solutions

Once PLA stereocomplex crystallites are formed in solu-

tion, they are insoluble in good solvents for either PLLA or

PDLA (e.g., chloroform, dichloromethane). This means

high stability of the stereocomplex crystallites compared

with that of homo-crystallites of either PLLAor PDLA. The

stereocomplex crystallites can be dissolved in extremely

good solvents at room temperature (e.g. 1,1,1,3,3,3-

hexafluoro-2-propanol) or in generally good solvents at

high temperatures near the boiling points (e.g., chloroform,

1,1,2,2-tetrachloroethane). However, the stereocomplex

crystallites become insoluble in extremely good solvents

even at elevated temperatures when the crystalline thick-

ness is high.

3.2.1. At a Fixed Polymer Concentration

The crystallites of a polymer are formed when the polymer

concentration in a solution exceeds a critical level. The

critical concentration for PLA stereocomplex crystallite

formation (stereocomplex crystallization) is much lower

than that for homo-crystallite formation of either PLLA or

PDLA (homo-crystallization). In other words, some good

solvents [e.g., chloroform and dichloromethane at room

temperature, acetonitrile around boiling temperature (ca.

80 8C)] for either PLLA or PDLA are poor solvents or non-

solvents for stereocomplex crystallites. Therefore, when an

initial polymer concentration is lower than the critical level

for homo-crystallite formation but higher than that for

stereocomplex crystallite formation, mixing two separately

prepared solutions of PLLA and PDLA results in the

formation of stereocomplex crystallites. Such stereocom-

plex crystallite formation induces particulate precipitates or

single crystals in dilute solutions (acetonitrile)[27] or gels in

Figure 17. Radius growth rate of shperulites (G) and inductionperiod of spherulite formation (ti) of PLLA, PDLA, and theirequimolarblendsasafunctionofcrystallizationtemperature(Tc).

[58]

582 H. Tsuji


concentrated solutions (chloroform, dichloromethane).[26]

The shape and size of stereocomplex precipitates in ace-

tonitrile depend on representative parameters: XD, polymer

concentration (Figure 14), molecular weights of PLLA and

PDLA, and temperature.[27] The stereocomplex particles

grow in a suspended state, which is monitored by the

turbidity of the solution (Figure 18).[27] After sedimentation

of the stereocomplex particles, the supernatant becomes

transparent again.

Probably, Murdoch and Loomis first observed gel forma-

tion upon PLA stereocomplexation.[62] Figure 19 shows a

phase diagram of a PLLA/PDLA/chloroform system.[21]

The lines between phases I and II and between phases II and

III are the critical concentrations for stereocomplex

crystallite formation (micro-gel formation) and macro-gel

formation, respectively. In stereocomplex gel formation,

the PLA stereocomplex crystalline regions act as physical

cross-links between the PLA chains (Figure 20).[24] In the

case of the PLA-based block copolymers mentioned below,

when the tie chains or sequences which do not take part in

the formation of cross-links or stereocomplex crystalline

regions are hydrophilic, the materials will be biodegradable

hydrogels in aqueous media. It is of great interest that

although L-lactyl unit sequences and D-lactyl unit sequences

become insoluble in water at a higher degree of polymer-

ization (DP), such hydrogels can be formed through

stereocomplexation in aqueous media upon mixing the

enantiomeric suspensions.

3.2.2. Casting (Increasing Polymer Concentrationby Solvent Evaporation)

In the solution castingmethod, solvent evaporation elevates

the polymer concentration of the solution from an initial

concentration to an infinite one. Therefore, during the

course of solvent evaporation, the polymer concentration

exceeds first the critical level of stereocomplex crystallite

formation, and then that of homo-crystallite formation. This

means that the stereocomplex crystallites are predomi-

nantly formed in equimolarly mixed solutions of PLLA and

PDLAwhen the solvent evaporation rate is sufficiently low.

Figure 18. Polymer concentration in supernatant of acetoni-trile solution as a function of time during stereocomplexation ofPDLA and PLLA [XD¼ 0.5, Mv (PLLA)¼ 4.2� 104 g �mol�1,Mv(PDLA)¼ 4.5� 104 g �mol�1, 1 g � dL�1, 80 8C].[27]

Figure 19. Phase diagram of PDLA/PLLA/chloroform system;homogeneous solution (I); cloudy solution containing stereo-complex microgel (II); stereocomplex macrogel (III). [XD¼ 0.5,Mv (PLLA)¼ 4.2� 104 g �mol�1, Mv(PDLA)¼ 4.5� 104 g �mol�1].[26]

Figure 20. SEM photograph and presumed structure of driedstereocomplex gel.[24]



However, rapid solvent evaporation will not give the stereo-

complex crystallites a sufficiently long time for their

formation, and the polymer concentration will reach the

critical level of homo-crystallite formation, resulting in the

formation of homo-crystallites. Homo-crystallization pre-

dominantly occurs when the molecular weights of both

PLLA and PDLA are high, the deviation of XD from 0.5 is

large, or the solvent evaporation rate is high. Figure 21

illustrates a typical example of the effects of PLAmolecular

weights on the kind and amount of the crystallites.[20] With

increasing the molecular weights of PLLA and PDLA, a

large fluctuation of microscopic XD from 0.5 occurs even in

an equimolarly mixed solution, due to the large radii of the

PLLA and PDLA molecules. This must retard the nuclei

formation and growth of stereocomplex crystallites, result-

ing in the formation of a large amount of homo-crystallites.

de Jong et al.[85,86] synthesized polydisperse L- and

D-lactic acid oligomers using stannous octoate and 2-(2-

methoxyethoxy)ethanol as initiator and coinitiator, respec-

tively, and subsequent preparative HPLC of polydisperse

oligomers yielded monodisperse oligomers (DP¼ 1–16).

They prepared nonblended and equimolarly blended speci-

mens by solution-casting with dichloromethane. DSC[85]

and WAXS[86] revealed that L- or D-oligomers were

crystallizable forDP above 11, while an equimolar mixture

formed stereocomplex crystallites forDP above 7,meaning

high stability of the stereocomplex crystallites compared

with that of homo-crystallites. However, WAXS analysis

revealed that the mixture of L- and D-lactic acid oligomers

(DP¼ 7) contained homo-crystallites as well as stereo-

complex crystallites. This may have arisen from epitaxial

crystallization of the homo-crystallites on the stereocom-

plex crystallites.[68]

3.2.3. Precipitation into Non-solvent

Amixed solution of PLLA and PDLA into a precipitant or a

non-solvent causes removal of the solvent from the solution

and diffusion of the non-solvent into the solution, resulting

in rapid crystallization. In this method, in addition to the

aforementioned representative parameters such as XD and

the molecular weights of PLLA and PDLA (Table 2), the

shear rate of the non-solvent and polymer concentration

affect greatly the kind and amount of crystallites formed. A

high shear rate of the non-solvent and a low polymer

concentration induce the predominant formation of stereo-

complex crystallites.[21]

3.2.4. Stepwise Assembly

Serizawa et al.[87] reported that stepwise assembly between

PLLA and PDLA on a quartz crystal microbalance (QCM)

substrate gave rise to stereocomplexation. Thiswas attained

by alternate immersion of the substrate into acetonitrile

solutions of PLLA and PDLA. They also indicated that the

assembly of PLLA can grow epitaxially on the surface of

stereocomplex crystallites, as shown by Brochu et al.[68]

4. Homo-Stereocomplexation

The reported examples for the PLA-based stereocomplex

from various types of polymer blends or from copolymers

are summarized in Table 4.

4.1. Stereocomplexation in Polymer Blend

4.1.1. Homopolymers

For homopolymer blends of PLLA and PDLA, intensive

studies have been carried out by Tsuji et al.[6,20–22,26,27,36]

and Murdoch and Loomis et al.,[62–66] with numerous

varying parameters. They found that the dominant para-

meters for stereocomplexation are XD and the molecular

weights of PLLA and PDLA. As stated earlier, the ratio of

stereocomplex crystallites to homo-crystallites decreases

with the deviation of XD from 0.5 (Figure 3) and increasing

molecular weights of PLLA and PDLA (Figure 21).

However, no crystallite formation occurs when the DP

values of PLLA and PDLA are lower than 7.[85]

4.1.2. Random Stereocopolymers

Tsuji and Ikada synthesized L-lactide-rich PLA and

D-lactide-rich PLA having optical purities from 0–100%

and traced the crystallization behavior of their nonblended

and blended films at different Tc from the melt[23] as well as

during solvent evaporation.[28] The DHm and Tm of stereo-

complex crystallites in blended films decreased with

decreasing optical purity (OP), in agreement with those of

homo-crystallites in nonblended films. It was found that

Figure 21. Enthalpies of melting (DHm) of stereocomplexcrystallites and homo-crystallites of equimolar (XD¼ 0.5)PLLA/PDLAblends prepared by solvent evaporation as a functionof the averaged viscosity-average molecular weight (Mav) ofPLLA and PDLA.[20]

584 H. Tsuji


Table4.

Stereocomplexation(racem

iccrystallization)oflacticacid-based

polymers.

Polymer

pairorpolymer

Initiator,catalystforsynthesis

oflacticacid

chains


iccrystallization)

Stereocomplexed

materials

Authorsandreferences

Procedure

Conditions

Param

eters

MonitoringMethods

Shape

Application

PLLA/PDLA

Stannousoctoate(Stannous

2-ethylhexanoate)/Lauryl

alcohol(1-D

odecanol)

Solution

Solvent:CHCl 3,

MolecularweightsofPLLAandPDLA,

L-and

D-Polymer

ratioand

concentration,Tem

perature,Tim

e

Viscometry,Testtube

tilting,1HNMR,DSC

Gels,Microgels

Tsujietal.[26]

Solvent:CH3CN


L-and

D-Polymer

ratioand

concentration,Tem

perature,Tim

e

DSC,Polarimetry,

SEM,13CNMR

Particles,Single

crystals

Tsujietal.[27,43]

Solvent:p-X

ylene

Fixed

WAXS,ED,TEM

Singlecrystals

Okiharaetal.[47,49]

ED,TEM

Singlecrystals

Cartier

etal.[61]

Casting

Solvent:CH2Cl 2,CHCl 3,

Benzene,Dioxane


L-and

D-Polymer

ratioand

concentration

DSC,POM,Tensiletesting

Films,Fibers

Tsujietal.[20,24,77]

Solvent:CH2Cl 2

L-and

D-Polymer

ratio

DSC,POM,SEM,GPC,

Tensiletesting

Films

Tsujietal.[132,134]

(HydrolyticDegradation)

Solvent:CHCl 3

Fixed

FT-IR

Films

Zhangetal.[53,54]

Precipitation

Solvent:CH2Cl 2,CHCl 3,Benzene,

Dioxane,Nonsolvent:CH3OH


L-and

D-polymer

ratioand

concentration,Tem

perature,

Rotationrateofnon-solvent

WAXS,DSC,SEM,

Tensiletesting

Fibrousprecipitates,

Fibers

Ikadaetal.,[4]Tsujietal.[21,77]

Bulk

Crystallizationfrom

themelt


L-and

D-Polymer

ratio,

Crystallizationtemperature

andtime

DSC,POM

Films

Tsujietal.,[22,58]

SasaiandYam

ane[144]

Takeupvelocity,Throughputrate,

Extrusiontemperature

WAXS,DSC,Tensile

testing

Fibers

Takasakietal.[141]


L-and

D-Polymer

ratio

DSC,GPC,Tensiletesting

Films

Tsuji,[19]TsujiandSuzuki[134]

(Hydrolyticdegradation)

Nucleators

DSC,POM

Films

Urayam

aetal.[70]

Amorphous–

madefrom

themelt

L-and

D-Polymer

ratio

Gravim

etry,GPC

Films

Tsuji[133](H

ydrolyticdegradation),

TsujiandMiyauchi[140]

(Enzymaticdegradation)

Inthemelt

L-and

D-Polymer

ratio

TG

Melts

TsujiandFukui[123]

(ThermalDegradation)

L-and

D-Polymer

ratio,

Concentrationofcatalyst

TG

Melts

Fan

etal.[128](Thermal

Degradation)

Oncompression

Fixed

PM-IRRAS

Langmuirfilm

sBourqueetal.,[75]

Pelletier

andPezolet[76]

Bulk,Solution

Solvent:CH3CN(Solution)

Fixed

ForceField

Sim

ulation,

WAXS,AFM

Films,Particles

Brizzolalaetal.[48]

Stepwiseassembly

Alternateim

mersioninto

polymer

solutions,Solvent:CH3CN

Polymer

concentrationandTem

perature,

Immersiontime

DSC,AFM

Thin

layer

Serizaw

aetal.[87,135]

(Alkalinedegradation)

Tem

plate

polymerization

MixingratioofDLAandPLLAorLLA

andPDLA,Tem

perature,Pressure,

Tim

e

DSC

Bulks

Spinuetal.[71–73]

Precipitation

Solvent:CH2Cl 2,Nonsolvent:CH3OH

MolecularweightsofPLLAandPDLA

DSC

Murdoch

andLoomis[42,62–66]

Zincpowder

Solution

Solvent:CH3CN

Fixed

IR,Ram

an,13CNMR

Kisteretal.[52]

Stannousoctoate/2-(2-M

ethoxy-

ethoxy)ethanol

Casting

Solvent:CH2Cl 2

MolecularweightsofPLLAandPDLA

DSC,WAXS

deJongetal.[85,86,100]

Diethylaluminum

ethoxide

Bulk

Crystallizationfrom

themelt

MolecularweightofPLLA,L-and

D-Polymer

ratio,Tem

perature

program

DSC,WAXS,POM

SchmidtandHillm

yer

[143]

L-lactide-rich

PLA/D-

lactid-richPLA

Stannousoctoate/Laurylalcohol

Casting

Solvent:CH2Cl 2

L/D-Lactideratioin

PLA

DSC

Films

Tsujietal.[28]

Bulk

Crystallizationfrom

themelt

Crystallizationtemperature,L/D-lactide

ratioin

PLA

DSC,POM

Films

Tsujietal.[23]

Aluminum

isopropoxide

Bulk

Crystallizationfrom

themelt

Coolingratefrom

themelt,

L/D-Lactide

ratioin

PLA,Mixingratioof

twopolymers

DSC,POM

Films

Brochuetal.[68]

AchiralSalenAlOMe

Precipitation


L/D-Lactideratioin

PLA

DSC

Spasskyetal.[110]

P(LLA-G

A)/P(D

LA-G

A)


Casting

Solvent:CH2Cl 2

Lactidecontentsin

copolymers

DSC

TsujiandIkada[29]

P(LLA-CL)/P(D

LA-CL)

Precipitation


Lactidecontentsin

copolymers

DSC

Murdoch

andLoomis[62–66]

PLLA-b-PCL/PDLA

Aluminum

tris(2-propanolate)

Al[OCH(CH3) 2] 3

Fixed

DSC

Dijkstra

etal.[89]

(Continued

)



Table4.

(Continued

)

Polymer

pairorpolymer

Initiator,catalystforsynthesis

oflacticacid

chains


iccrystallization)

Stereocomplexed

materials

Authorsandreferences

Procedure

Conditions

Param

eters

MonitoringMethods

Shape

Application

PLLA-b-PCL/PDLA-b-PCL

Yttrium

isopropoxide

Precipitation

Solvent:CHCl 3,N

onsolvent:C2H5OC2H5

MolecularweightofPLAblock

DSC

Stevelsetal.[90]

Stannousoctoate

Precipitation


MolecularweightsofPLAand

PCLblocks

DSC

Pensecetal.[91]

Yttrium

alkoxide

Solution

Solvent:THF

Polymer

concentration,Tem

perature

LS,DSC,1HNMR,IR

Portinhaetal.[56,57]

PLLA-b-PCL-b-PLLA/

PDLA-b-PCL-b-PDLA

Stannousoctoate

Precipitation


Fixed

DSC

Pensecetal.[91]

PLLA-b-PEG/PDLA-b-PEG

Notspecified

Solution

Solvent:CH3CN

Fixed

WAXD,AFM

Particles

Brizzolara

etal.[50]

PLLA-b-PEG-b-PLLA/

PDLA-b-PEG-b-PDLA

Stannousoctoate/PEG

Precipitationor

Casting

Solvent:CHCl 3,Nonsolvent:Hexane

PercentageorMolecularweightofPLLA

orPDLA

DSC

Precipitates,

Films

Stevelsetal.[92]

Precipitation

Solvent:CH2Cl 2,Nonsolvent:H2O

Fixed

DSC,X-ray

Particles

DDS

Lim

andPark[93]

Casting

Solvent:THF/H

2O(v/v)¼1/2,THF

was

removed

PercentageorMolecularweightofPLLA

orPDLA,Tem

perature

Testtubetilting,Visible

lighttransm

ittance,

WAXS,Rheological

measurements

Gels

Fujiwaraetal.[94]

PLLA-b-PEG-b-PLLA/

PDLA-b-PEG-b-PDLA

andPLLA-b-PEG/PDLA-

b-PEG

Zincpowder/PEG

Solution

Solvent:H2O

MolecularweightsofPLAand

PEGblocks,Tem

perature,Tim

eDSC,WAXS,Ram

anspectroscopy,

Viscoelasticity

Gels

LiandVert[95,96]

PLLA-b-PSA-b-PLLA/

PDLA-b-PSA-b-PDLA

Polycondensation/PSA

Casting(Solution

andmelt)

Solvent:CH2Cl 2

MolecularweightsofPLAandPSA

blocks,Polymer

mixingratio

DSC,SEM

Powder

DDS

SlivniakandDomb[97]

dextran-graft-PLLA/

dextran-graft-PDLA

Stannousoctoate/

2-(2-M

ethoxy-

ethoxy)ethanol

Solution

Solvent:Acetate-buffered

solution(pH4)

Degreeofsubstitution(D

S),Molecular

weightsofPLLAandPDLAchains

Storagemodulus,

FT-IR,Swellingratio

Gels

DDS

deJongetal.[86,99–102]

Poly(H

EMA-graft-oligo

L-lactie)/Poly(H

EMA-

graft-oligo

L-lactie)

Stannousoctoate/HEMA

Casting

CHCl 3

MolecularweightsofL-orD-lactide

sidechains

DSC,WAXS

Films

Lim

etal.[98]

pHPMAm-graft-L-lacticacid

oligomers/pHPMAm-

graft- D-lacticacid

oligomers

Stannousoctoate/2-(2-M

ethoxy-

ethoxy)ethanol

Solution

Solvent:Acetatebuffer

(pH4)

Degreeofsubstitution(D

S),molecular

weightsofPLLAandPDLAchains

Rheological

measurements,Swelling

Gels

van

Nostrum

[103]

PMBLLA/PMBDLA


Solution

Solvent:CH3OH/CH2Cl 2/(v/v)¼2/1,

inthepresence

ofNaC

lMolecularweightsofL-orD-lactide

sidechains

DSC,WAXS

Porousfilm

sScaffold

WatanabeandIshiharaetal.[104–106]

PLLA-grafted

film

/PDLA

Stannousoctoate

Solution

Solvent:CH3CN,CHCl 3

MolecularweightsofL-lactide

sidechains,Solvent

FT-IR,WAXS

Films

Tretinnikovetal.[107]

Stereo-block

PLA

Aluminum

tris(2-propanolate)

Al[OCH(CH3) 2] 3

Precipitation

Solvent:Toluene,Nonsolvent:CH3OH

Fixed

DSC

Yuietal.,[108]Dijkstra

etal.[89]

Rac-(SalBinap)A

lOi Pr

Precipitation

Solvent:CH2Cl 2Nonsolvent:CH3OH

Fixed

DSC

Ovittetal.[114,115]

Fixed

DSC

Radanoetal.[113]

(-)-(SalBinap)A

lOMe

Initiator/Monomer

ratio,Reactiontime

DSC

Spasskyetal.[109,110]

AchiralSalenAlOMe

Aspolymerized,

Bulkfromthemelt

D/L-Lactideratio;Crystallization

temperature

andtime,Coolingrate

from

themelt

DSC,WAXS,POM

Wiesniwskietal.,[111]

Sarasuaetal.[112]

SnCl 2(Polycondensation)

As-polymerized

Molecularweightsofhomopolymersof

PLLAandPDLA,Reaction

temperature

andtime

DSC,WAXS

Fukushim

aetal.[116]

Poly(L-lactide-co-D-lactide)

(62.5/37.5),(50/50)

Zincpowder,Stannousoctoate,

orPolymersweresupplied

Bulk

during

hydrolytic

degradation

Catalystforsynthesis,Hydrolysismedia,

Tem

perature,Tim

eDSC,WAXS

Plates,Films

LiandVert[78–82]

PDLA/LHRH,

PDLA/Vapreotide

Stannousoctoate

Solution

Solvent:CH3CN

Polymer

mixingratio

DSC,SEM

Particles

DDS

Slager

etal.[117]

PDLA/Leuproide,PDLA/

Vapreotide

Stannousoctoate/(Benzyl

alcohol)

Solution,Casting

Solvent:CH3CN

Tim

e,Polymer

mixingratio,Molecular

weightofPLA

DSC,SAXS,SEM,AFM,

Cryo-TEM,Confocal

microscopy

Particles

DDS

Slager

etal.[118–121]

PDLA/Insulin,PDLA-b-

PEG/Insulin,

PDLA-b-PEG-b-PDLA/

Insulin

Stannousoctoate/Octanol

Solution

Solvent:CH3CN

Fixed

DSC,SEM,HPLC

Particles

DDS

Slager

andDomb[122]

586 H. Tsuji


stereocomplex crystallites in blendedfilms aswell as homo-

crystallites in nonblended films can be formed as long as

both L-lactide-rich PLA and D-lactide-rich PLA have OP

values above 76% (XD� 0.88,XD� 0.12) (Figure 22). Only

in this section is XD used as D-lactide unit content in a

copolymer according to the following definition:

XD¼Weight of D-lactide=Weight of L- and D-lactide

ð2Þ

The L-lactyl unit sequence length (lL) and D-lactyl unit

sequence length (lD) can be calculated fromXD values using

Equation (3) and (4):[88]

lL ¼ 2=XD ð3Þ

lD ¼ 2=ð1� XDÞ ð4Þ

These equations assume that L-lactide and D-lactide were

polymerized by their random addition and that no ester

exchange reaction occurred during polymerization and

thermal treatment. Figure 22 and Equation (2)–(4) indicate

that for the solution-casting method at least 16.4 L-lactyl

unit sequences and D-lactyl unit sequences are required for

PLA stereocomplexation (stereocomplex crystallization)

and homo-crystallization,[28] in agreement with the results

for the melt-crystallization method.[23] The critical se-

quence unit value is slightly higher than the 7 lactyl units for

pairs of the L-lactic acid oligomer and D-lactic acid

oligomer.[85] In the case of melt-crystallization, by crystal-

lization from the melt at temperatures between the Tmvalues of stereocomplex crystallites and homo-crystallites

(between the solid line and dashed/single dotted line for

blended specimens in Figure 23), well-stereocomplexed

PLA materials can be prepared.[23] On the other hand,

Brochu et al.[68] synthesized PLLA, PDLA, and poly(L-

lactide-co-D-lactide) [P(LLA-DLA)](20/80) and investi-

gated stereocomplexation between PLLA and P(LLA-

DLA)(20/80) as well as that between PLLA and PDLA

during cooling from the melt under various mixing ratios of

the two polymers.

4.1.3. Hetero Random Copolymers

Murdoch and Loomis reported the effects of incorporated

e-caprolactone units on PLA stereocomplexation by pre-

paring equimolar blends of poly(L-lactide-co-e-caprolac-tone) [P(LLA-CL)] and poly(D-lactide-co-e-caprolactone)[P(DLA-CL)][62] having e-caprolactone unit content of upto 32 wt%. The Tm of the stereocomplex decreased with

increasing the e-caprolactone unit content. However, the

critical lactyl unit sequence length for stereocomplexation

was not identified. By a procedure similar to that in Section

4.1.2., Tsuji and Ikada[29] studied the effects of incorporated

glycolyl unit (a half glycolide unit) content on PLA

stereocomplexation. The DHm and Tm of stereocomplex

crystallites in equimolarly (XD¼ 0.5) blended films

decreased with increasing glycolyl unit content, in agree-

ment with those of homo-crystallites in nonblended films.

The stereocomplex crystallites in blended films of poly(L-

lactide-co-glycolide) [P(LLA-GA)] and poly(D-lactide-co-

glycolide) [P(LDA-GA)] are formed with L- and D-lactide

unit content as low as 72.1 and 68.6 wt%, respectively,

Figure 22. Amorphous (A), stereocomplex crystalline (S), andhomo-crystalline (H) phases in as-cast binary equimolar (1:1)blends from PLAs with different D-lactide contents [XD¼D-lactide/(L-lactideþ D-lactide)].[28]

Figure 23. Amorphous (A), stereocomplex crystalline (S), andhomo-crystalline (H) phases in equimolarly blended and non-blended PLA films crystallized from the melt as a function ofoptical purity (OP); highest crystallization (annealing) temper-ature below which stereocomplexation occurs (Tc,s) in equimo-larly (1:1) blended PLAs (solid line) and highest crystallizationtemperature below which homo-crystallization occurs (Tc,h) inequimolarly blended PLAs (dashed/single dotted line) andnonblended PLAs (dashed line).[23]



whereas the homo-crystallites in nonblended films are

formed with L- or D-lactyl unit content above 81.0 wt%

(Figure 24). The calculated critical L- or D-lactyl unit

sequence length for stereocomplex crystallization in the

blended films (5.5 lactyl units) is lower than 8.8 lactyl units

for homo-crystallites in the nonblended films, reflecting the

fact that the peculiarly strong interaction between the L-

lactyl unit sequences and D-lactyl unit sequences enhances

the stability of stereocomplex crystallites and the crystal-

lizablity of the blended films. Here, the calculation proce-

dure for the lactyl unit sequence length is similar to the

Equation (3) and (4), and is given in our recent article.[88]

This value of 5.5 lactyl units is slightly lower than the

7 lactyl units for pairs of the L-lactic acid oligomer and

D-lactic acid oligomer.[85] It should be noted that the critical

values shown here are average values and, therefore, the

copolymers contain L- or D-lactyl unit sequences longer

than the average values. The critical value for the lactide-

glycolide copolymer is lower than that for random lactide

stereocopolymers (Section 4.1.2.), suggesting that the

glycolide units in the copolymers must have enhanced the

stereocomplexation between L-lactyl unit sequences and D-

lactyl unit sequences. It seems probable that the lower steric

hindrance of the methylene group of glycolyl units

(compared with the high steric hindrance of the ethylidene

group of L-lactyl or D-lactyl units) raises the chain mobility

of glycolide copolymers, resulting in high stereocomplex-

ationability during solvent evaporation.

4.1.4. Hetero Block Copolymers

4.1.4(a). With Poly(e-caprolactone) (PCL) Blocks

Dijkstra et al.[89] prepared an A-B diblock copolymer

[number-average molecular weight (Mn)¼ 3.87� 104 g �

mol�1] of PLLA (A) and PCL (B) as well as PDLA

(Mn ¼ 9.7� 103 g �mol�1). They indicated that PLA stereo-

complexation takes place even in the presence of polymeric

impurity of a PCL block. In this blend, e-caprolactone unitsequences were phase-separated to form their crystalline

regions.

Stevels et al.[90] synthesized A-B diblock copolymers of

PLLA or PDLA (DP¼ 1–80) (A) and PCL (DP¼ 70) (B).

Upon blending PLLA-b-PCL and PDLA-b-PCL, both

having weight fractions of PLA blocks above 44%, a Tmincrease (ca. 55 8C) of the PLA crystalline regions was

observed due to stereocomplexation, while for the blends

composed of PLLA-b-PCL and PDLA-b-PCL, both having

weight fractions of PLA blocks below 22%, no melting of

the PLA crystalline regions was observed, meaning that the

PLA blocks were noncrystallizable. On the other hand,

crystallization of PCL blocks took place in the blended

specimens aswell as in the nonblended specimens. Portinha

et al.[56] prepared A-B diblock copolymers of PLLA or

PDLA (A) and PCL (B) and monitored their aggregation

behavior in nonblended and blended THF solutions. The

hydrodynamic radii of assemblies in enantiomeric blended

solutions were 200 nm, which were higher than those in

nonblended polymer solutions. The radius distribution in

enantiomeric blend solutions was sharper than that of non-

blended polymer solutions. Furthermore, the same research

group[57] continued studies on the self-assembly of PLLA-

b-PCL and PDLA-b-PCL in THF by the use of DSC,

dynamic LSmeasurements, 1HNMRspectroscopy, and FT-

IR. They revealed that, at higher concentrations such as

10 g � dL�1, stereocomplexation was in competition with a

solvophobically driven aggregation, whereas at lower con-

centrations, only the stereocomplexation process was

involved.

Figure 24. Schematic representation for the phases and Tm in Blend 11 [nonblend P(DLA-GA), Blend 31 and 32 [blended films from PDLA and P(DLA-GA)] (a), Blend 2 [blendedfilms from P(LLA-GA) and P(DLA-GA)], Blend 41 [blended films from PDLA and P(LLA-GA)], and Blend 42 [blended films from PLLA and P(DLA-GA)] (b).[29] The areas withhorizontal stripes, vertical stripes, both horizontal and vertical stripes, and without stripesmeans homo-crystallineþ amorphous, stereocomplex crystallineþ amorphous, stereocom-plex crystallineþ homo-crystallineþ amorphous, and amorphous, respectively. Tm1 andTm2 are the Tm of homo-crystallites and stereocomplex crystallites, respectively.

588 H. Tsuji


Pensec et al.[91] synthesized A-B-A triblock copolymers

of PLLA or PDLA (DP¼ 58) (A) and PCL (DP¼ 34) (B)

and A-B diblock copolymers of PLLA (DP¼ 19–54) or

PDLA (DP¼ 20–57) (A) and PCL (DP¼ 24–106) (B).

They indicated that stereocomplexation occurred in all

enantiomeric polymer pairs precipitated from a dichlor-

omethane solution into methanol. The DHm and Tm of

stereocomplex crystallites were affected by the L-lactyl unit

sequence length and D-lactyl unit sequence length, but were

not affected by the e-caprolactone sequence length.

4.1.4(b). With Poly(ethylene glycol) (PEG) Blocks

Brizzolara et al.[50] prepared A-B diblock copolymers

(Mn ¼ 5.6� 104 and 5.9� 104 g �mol�1) of PLLAor PDLA

(A) and PEG (B). The molecular weight ratio of the PLA

block to the PEG block was 1.5/1. They traced stereo-

complexation between enantiomeric copolymer blends by

WAXS, and the difference in the morphology between

precipitates of nonblended and blended specimens by

AFM.

Stevels et al.[92] synthesized A-B-A triblock copolymers

(Mn ¼ 6.7� 103–2.3� 104 g �mol�1, PEG content 27–

86 wt%) of PLLA or PDLA (A) and PEG (Mn ¼ 6 000) (B)

and prepared equimolarmixtures of PLLA-b-PEG-b-PLLA

and PDLA-b-PEG-PDLA by two different procedures,

precipitation and solution-casting. Although they investi-

gated the effects of the procedures on stereocomplexation

as reported for the blends from pure PLLA and PDLA,[20,21]

stereocomplexation occurred readily in specimens prepared

by these two different procedures. Probably, the molecular

weights of the block copolymers were sufficiently low to

form stereocomplex crystallites, irrespective of the proce-

dure. Another probable explanation is that the PEG seg-

ments acted as a plasticizer for the PLA segments and

consequently enhanced stereocomplexation of the block

copolymers. On the other hand, Lim and Park[93] prepared

A-B-A triblock copolymers of PLLA (DP¼ 200, 250) or

PDLA (DP¼ 208, 262) (A) and PEG (DP¼ 23, 77) (B).

Stereocomplexation between the enantiomeric block copo-

lymers was traced by DSC and WAXS. The cumulative

release of bovine serum albumin (BSA) was lower for

stereocomplexed microspheres than for those of non-

blended blockcopolymers, when compared with the same

period. Furthermore, Fujiwara et al.[94] prepared synthe-

sized A-B-A triblock copolymers (Mn ¼ 7 200 and 6 800 g �mol�1) of PLLA or PDLA (A) and PEG (Mn ¼ 4 600 g �mol�1) (B). The enantiomeric triblock copolymers were

separately dissolved in tetrahydrofuran (THF)/water (v/

v)¼ 1/2 and then THF was removed by evaporation,

leaving 10 wt.-% aqueous dispersion. They traced stereo-

complexation between the enantiomeric triblock copoly-

mers upon heating the aqueous dispersion from room

temperature to 37 8C by rheological measurements, the test

tube tilting method, and WAXS.

Li and Vert[95,96] synthesized A-B diblock and A-B-A

triblock copolymers of PLLA or PDLA (DP¼ 12–

52, molar mass¼ 860–3 700) (A) and PEG (DP¼ 104–

454, molar mass¼ 4 600–20 000) (B). The crystallization

of PEG was dominant in these block copolymers. On

blending the enantiomeric block copolymers in an aqueous

medium, gels were formed, as seen for the homopolymer

blends of PLLA and PDLA in organic solvents.[26,62] Such

stereocomplexation was confirmed by Raman spectro-

scopy, WAXS, and rheological measurements.[95,96]

4.1.4(c). With Poly(sebacic acid) (PSA) Blocks

Slivniak and Domb[97] synthesized A-B-A triblock copo-

lymers of PLLA or PDLA (DP¼ 20–30) (A) and PSA

(DP¼ 2–40) (B) and observed stereocomplexation

between these enantiomeric block copolymers.

4.1.5. Graft Copolymers

Lim et al.[98] prepared poly[2-hydroxyethyl methacrylate-

graft-oligo(L-lactide)] and poly[2-hydroxyethyl methacry-

late-graft-oligo(D-lactide)] by radical polymerization of

macromonomers 2-hydroxyethyl methacrylate-graft-

oligo(L-lactide) and 2-hydroxyethyl methacrylate-graft-

oligo(D-lactide), respectively, in the presence of 2,20-azoisobutyronitrile (AIBN). The macromonomers were

synthesized by ring-opening polymerization of L- or

D-lactide in the presence of stannous octoate and 2-

hydroxyethyl methacrylate as initiator and coinitiator, res-

pectively. Stereocomplexation occurred during solution-

casting of mixed solutions of enantiomeric graft polymers.

The stereocomplexed films became hydrogels in aqueous

media.

de Jong et al.[86,99–102] synthesized dextran [degree of

substitution (DS, number of lactic acid side chains per 100

glucopyranose units)¼ 3–17]-graft-L-(or D-)lactic acid

oligomers [average degree of polymerization (DPav)¼ 6–

12] by forming a carbonate bond using N,N0-carbonyldii-midazole (CDI) and monitored their stereocomplexation in

an acetate-buffered solution (100� 10�3M, pH 4) by

rheological measurements. Here, lactic acid oligomers

were synthesized by ring-opening polymerization of LLA

or DLA using stannous octoate and 2-(2-methoxyethoxy)

ethanol (MEE) as initiator and coinitiator, respectively.

At 20 8C the storage modulus (G0) of dextran-graft-

enantiomeric lactic acid oligomers increased with time due

to the formation of crosslinks composed of stereocomplex

crystallites, but decreased upon heating to 80 8C due to their

melting. They confirmed stereocomplexation by FT-IR[99]

as well as WAXS.[57] The properties of stereocomplexed

hydrogel can be manipulated by alteringDP andDS. It was

found that at least 11 lactyl units are required to obtain a

stereocomplexed hydrogel.[99] These results are summar-

ized in detail in their review article.[101] Furthermore, the

same research group, van Nostrum et al.[103] prepared



poly(2-hydroxypropylmethacrylamide) (pHPMAm)-graft-

L-(or D-)lactic acid oligomers by forming an ester linkage

using AIBN. The gels were formed from pHPMAm-graft-

enantiomeric L- and D-lactic acid oligomers in an acetate-

buffered solution (pH 4) as evidenced by rheological

measurements (G0).Watanabe and Ishihara et al.[104–106] synthesized graft–

type copolymers containing L-lactide unit sequences or D-

lactide sequences as side-chains (PMBLLA and PMBDLA,

respectively) by copolymerization of 2-methacryloylox-

yethyl phosphorylcholine (MPC), butyl methacrylate, and

PLLA or PDLA macromonomers. They prepared porous

stereocomplexed films using an extraction method with

water-soluble particles of NaCl.[104] On the other hand,

Tretinnikov et al.[107] synthesized graft layers of PLLAwith

thicknesses from 7 to 35 nm from hydroxy end-groups of a

self-assembled monolayer on gold and monitored the

stereocomplexation between free PDLA and grafted PLLA

chains on the surface by the use of WAXS and FT-IR. In

other words, PDLAmoleculeswere effectively adsorbed on

or entrapped by the PLLA-grafted surface.

4.2. Stereocomplexation in Nonblended Polymers

4.2.1. Stereo-Block Copolymers

Yui et al.[108] and Dijkstra et al.[89] synthesized A-B diblock

copolymers of PLLA (A) and PDLA (B) having L-lactyl

unit content of from 82 to 37% through a ring-opening

sequential two-step polymerization of L- and D-lactide

[Figure 1(e)] initiated by aluminum tris(2-propanolate)

Al[OCH(CH3)2]3. Although they observed stereocom-

plexation between L-lactyl unit sequences and D-lactyl unit

sequences in a block copolymer (Mn ¼ 2.01� 104 g �mol�1) even with L-lactide unit content of 55%, further

investigation on the block copolymers has not been reported

so far.

Spassky et al.,[109,110] Wisniewski et al.,[111] Sarasua

et al.,[112] Radano et al.,[113] and Ovitt and Coates[114,115]

synthesized highly isotactic stereo-block copolymers from

lactides with relatively low optical purities in one step

[Figure 1(f)] using Schiff’s base/aluminum alkoxide

initiators, [(�)-(Salbinap)AlOMe],[109,110] achiral Sale-

nAlOMe,[111,112] or racemic [(Salbinap)AlOiPr].[113–115]

They traced stereocomplexation in the stereo-block copo-

lymers by DSC, WAXS, and/or POM. Sarasua et al.[112]

showed that stereocomplexation of PLAwith [a]58925 of�66,

�73, and �95 deg � dm�1 � g�1 � cm3 in chloroform can

occur when the crystallization temperature and time are

carefully selected.

Fukushima et al.[116] proposed a novel procedure to

synthesize stereo-block PLA by solid-state polycondensa-

tion of a stereocomplexed mixture of PLLA and PDLA. In

the first step, homopolymers PLLA and PDLA having 2.0–

4.6� 104 g �mol�1 were prepared; in the second step the

enantiomeric homopolymers were melt-mixed to form

stereocomplex crystallites; in the third step further poly-

condensation of the stereocomplexed mixture was carried

out.

4.2.2. Random Stereo Copolymers

Normally, in marked contrast to stereo-block copolymers

and blends between L-lactide-rich PLA and D-lactide-rich

PLA, no stereocomplexation occurs in relatively random

stereo copolymers during materials preparation. However,

Li et al. found steteocomplexation between L-lactyl unit

sequences and D-lactyl unit sequences in poly(L-lactide-co-

D-lactide)(62.5/37.5),[78] poly(L-lactide-co-D-lactide)(50/

50) (i.e. PDLLA) prepared with zinc powder,[79] PDLLA

prepared with stannous octoate,[80] and supplied

PDLLA,[81] when thick plates of these copolymers were

hydrolyzed to a great extent in a phosphate-buffered solu-

tion at 37 8C for 30 and 17 weeks, in an aqueous solution

with a caffeine base for 27 weeks, and in a phosphate-

buffered solution at 60 8C for 4 weeks, respectively.

Stereocomplexation took place in a shorter period for plate

specimens than for film specimens,[81] reflecting the fact

that accelerated hydrolytic degradation at the core parts of

the plates enhances stereocomplexation. They suggested

that although the initial fractions of L-lactyl unit sequences

and D-lactyl unit sequences having high sequence numbers

are low in these copolymers, the fractions will be increased

by selective hydrolysis and removal of chains with

relatively random sequences, resulting in stetreocomplexa-

tion. Stereocomplexation can be ascribed to the predomi-

nantly isotactic structure of the copolymers obtained by

ring-opening polymerization of lactides with low optical

purities. Schwach et al.[82] investigated the effects of the

kinds of catalysts on stereocomplexation aswell as tacticity,

water uptake, weight loss, and release of acids. It was

demonstrated that stereocomplexation during hydrolytic

degradation was not influenced by the kind of catalyst and

that PDLLA synthesized with stannous octoate had a

predominantly isotactic structure.

5. Hetero-Stereocomplexation

In the previous sections, stereocomplexation is restricted to

that between L-lactyl unit sequences and D-lactyl unit

sequences (homo-stereocomplexation). In this section,

stereocomplexation between the PDLA and the L-enantio-

meric form of an optically active polymer or between PLLA

and the D-enantiomeric form of another kind of optically

active polymer (hetero-stereocomplexation) is described.

Slager andDomb et al. reported hetereo-stereocomplexa-

tion between PDLA and L-configured peptides such as the

luteinizing hormone-releasing hormone (LHRH),[117] leu-

proide (an LHRH nonapeptides analogue),[118–121]

and vapreotide (a cyclic octapeptide somatostatin

590 H. Tsuji


analogue)[117–119]. Hetero-stereocomplexation was

observed by the use of DSC,[117,120] SEM,[117–120]

SAXS,[118,119] cryogenic transmission electronmicroscopy

(Cryo-TEM),[118,119] and confocal microscopy.[120] In

addition to DSC results, the increase in scattering intensity

in SAXS suggested the formation of hetero-stereocomplex

particles, which was further evidenced by SEM and

Cryo-TEM and confocal microscopic photographs. The

stereocomplex particles had amean unweighed particle size

of 1.7 mm.[119]

L-Insulin and PDLA form stereocomplex porous parti-

culate precipitates and become insoluble in acetonitrile

which dissolves isotactic PLLA or PDLA at an elevated

temperature.[122] The results of DSCmeasurements and the

fact that after the formation of particles no free insulin was

detected by HPLC supported their hetero-stereocomplexa-

tion. They also prepared hetero-stereocomplexed particles

for drug delivery systems (DDS) of insulin with PDLA,

PDLA-b-PEG, PDLA-b-PEG-PDLA, PLLA/PDLA, or

PLLA-b-PEG/PDLA-b-PEG. When insulin, D-lactyl unit

sequences, and L-lactyl unit sequences were involved in a

system, two types of stereocomplex can be formed, i.e., a

homo-stereocomplex and a hetero-stereocomplex.

On the other hand, Force-Field simulation predicted that

PLLA [(�)-PLA] can form a hetero-stereocomplex with

(þ)-alternating isotactic propylene-CO-copolymers [P(P-

alt-CO)] and vice versa.[50] However, Brizzolara et al. have

not yet shown experimental evidence for hetero-stereo-

complexation.

6. Degradation

6.1. Thermal Degradation

Tsuji and Fukui performed a thermogravimetric study on an

equimolar (XD¼ 0.5) blend of PLLA and PDLA as well as

nonblended PLLA and PDLA.[123] These polymers were

synthesized with stannous octoate (0.03 wt%, Sn con-

tent< 88 ppm) and lauryl alcohol (0.5 wt% for PLLA,

0.4 wt% for PDLA) and purified by precipitation using

methylene chloride and methanol, as solvent and non-

solvent, respectively. The initial Mn values of PLLA and

PDLA before thermal degradation were 8.7� 104 and

9.5� 104 g �mol�1, respectively. In heat scanning at a cons-

tant rate in thermogravimetry (TG), a very small difference

was observed between the TG curves of the specimens,

whereas at fixed temperatures of 250 and 260 8C exceeding

the Tm of the stereocomplex, i.e. in the melt, the equimolar

blend has higher stability than the nonblended PLLA or

PDLA (Figure 25). It is expected that the 31 helical

conformation remains even in the melt of the blend at

temperatures exceeding the Tm of the stereocomplex and,

therefore, the peculiarly strong interaction between

L-lactide chains and D-lactide chains has a significant effect

in reducing the molecular mobility and, therefore, in

disturbing the thermal degradation. However, it seems that,

at temperatures far higher than the Tm of the stereocomplex,

such peculiar interaction arising from the helical conforma-

tion disappears, resulting in a small difference in thermal

stability between nonblended and blended films. The

activation energy for the thermal degradation (DEtd) values

was estimated by the method recommended byMacCallum

et al.[124–127] The obtained DEtd value of the equimolar

blend was in the range of 205–297 kJ �mol�1, which was

higher by 82–110 kJ �mol�1 than the averaged DEtd values

of nonblended PLLA and PDLA (87–104 kJ �mol�1).[123]

On the other hand, Fan et al.[128] reported DEtd values of

80–100, 100–120, and 125–180 kJ �mol�1 respectively for

as-polymerized (Sn content: 286 ppm), purified by preci-

pitation with methanol (Sn content: 266 ppm), and purified

metal-free (Sn content < 10 ppm) equimolar blend speci-

mens from PLLA (Mn ¼ 1.2–1.3� 105 g �mol�1) and

PDLA (Mn ¼ 1.2–1.3� 105 g �mol�1). The thermal degra-

dation of the three specimens proceeds through mechan-

Figure 25. The percentage of remaining weight of the filmsmeasured isothermally at the constant temperature as a function ofheating time.[123] Here, L, D, L/D represent nonblended PLLA andPDLA films, and their equimolarly blended film, respectively.



isms of unzipping caused by the Sn-alkoxide chain end,

Sn-catalyzed selective lactide elimination, and random

degradation, respectively. In our study, constant temper-

ature analysis was made in the temperature range where

PLLAandPDLAhave a peculiarly strong interaction,while

Fan et al. analyzed the specimens under constant heating,

and the procedure for DEtd estimation is different from our

case.[129–131] The DEtd value difference between the two

articles (ours and Fan et al.) is attributable to the differences

in initial molecular weights and terminal groups of PLLA

and PDLA, the kind and concentration of the remaining

catalyst, and the method and procedure forDEtd estimation.

6.2. Hydrolytic Degradation

Tsuji found that stereocomplexed PLA specimens have a

higher hydrolysis-resistance compared with that of non-

blended PLLA and PDLA specimens when they were

hydrolyzed in a phosphate-buffered solution at pH 7.4 and

37 8C (Figure 26).[132] It is surprising that although the

decrease in tensile strength of the nonblended specimens

started even at 4 months, the stereocomplex specimens

retained their initial tensile strength for a long period of

16 months. Similarly, de Jong et al.[100] reported hydrolytic

degradation of solution-cast L-lactic acid oligomers

(DP¼ 7) and the stereocomplex of L- and D-lactic acid

oligomers (DP¼ 7) at pH7 and 37 8C.They showed that thefraction of the L-lactic acid oligomer approached nil within

4 h, whereas 50% of the stereocomplex remained even after

96 h of degradation. Here, although the L-(or D-)lactic acid

oligomer and stereocomplex are amorphous and crystalline,

respectively, the obtained results are in agreement with our

results.[132] Such stereocomplex crystallization should have

disturbed the hydrolytic degradation of stereocomplexed

specimens compared with that of the L-lactic acid oligomer.

However, hydrolytic degradation proceeds predominantly

in the amorphous regions between the stereocomplex

crystalline regions. This means that the PLLA chains and

PDLA chains should have a peculiarly strong interaction

even when they are in an amorphous state, as suggested by

the aforementioned thermal degradation results.[123] To

confirm this assumption, we prepared various types of equi-

molarly blended specimens from PLLA and PDLA, i.e.,

amorphous-made[133] and homo-crystallized,[19] and car-

ried out their hydrolytic degradation in a phosphate-

buffered solution at pH 7.4 and 37 8C, together with

nonblended PLLA and PDLA specimens. We observed

retarded hydrolytic degradation of the blended specimens

compared with the nonblended specimens, irrespective of

their state, amorphous or homo-crystallized, reinforcing the

abovementioned hypothesis. Tsuji and Suzuki[134] carried

out the hydrolytic degradation of stereocomplexed fibers

and films and revealed that the morphology of the stereo-

complexedmaterials have crucial effects on their hydrolytic

degradation rates.

There have been some reports that stereocomplexa-

tion between enantiomeric L-lactide unit sequences and

D-lactide unit sequences retarded hydrolytic degradation;

e.g., poly[2-hydroxyethyl methacrylate-graft-oligo(lac-

tide)] (Lim et al.[98]) and A-B-A triblock copolymers of

Figure 26. Weight remaining (a),Mn (b), and tensile strength (c)of nonblended films and well-stereocomplexed blended film ofPLLA and PDLA films after hydrolytic degradation in phosphate-buffered solution (pH 7.4, 37 8C).[132]

592 H. Tsuji


PLA (A) with poly(sebacic acid) (PSA) (B) (Slivniak and

Domb[97]). On the other hand, de Jong et al.[102] indicated

that hydrolytic degradation of the stereocomplex hydrogels

from dextran (DS¼ 3–12)-graft-L- and D-lactic acid oligo-

mers (DP¼ 6–12) depends on the number of lactate grafts

(DS), the length (DP) and polydispersity of the grafts, and

the initial water content, and that the degradation time

varied from one to seven days. Moreover, van Nostrum

et al.[103] showed that the hydrolytic degradation time of the

stereocomplex hydrogels from poly(2-hydroxypropyl-

methacrylamide) (pHPMAm)-graft-L- and D-lactic acid

oligomers can be readily tailored from 1 week to almost

3 weeks by changing the grafting density of the polymers

and the structure of the terminal group of the side chains.

6.3. Alkaline Degradation

Serizawa et al.[135] prepared the PLA stereocomplex assem-

bly and the assemblies composed of both a stereocomplex

crystalline layer and a PLLA homo-crystalline layer

deposited on QCM substrates by the procedure stated

earlier (Section 3.2.4), and their alkaline hydrolytic degra-

dation rates were investigated. They claimed that the

hydrolysis-resistance of the PLLA crystalline layer having

a 103 helical conformation is higher than the stereocomplex

layer having a 31 helical conformation, in marked contrast

to the abovementioned results in neutral media (Section

6.2).

6.4. Enzymatic Degradation

Proteinase K is an endo-protease having broad specificity

but with preference for the cleavage of the peptide bond

C-terminal to aliphatic and aromatic amino acids, espe-

cially alanine.[136] The similar chemical structures of lactic

acid and alanine are expected to induce the proteinase

K-catalyzed hydrolysis of the C-terminal of PLLA or

L-lactyl unit sequences. As already found, proteinase K can

catalyze the hydrolytic degradation of L-lactyl chains in

amorphous regions.[137,138] The tie chains and chains with a

long free end in amorphous regions can be enzymatically

cleaved, whereas the folding chains and the chains with a

short free end are highly resistant to enzymatic clea-

vage.[139] Since hydrolytic degradation proceeds predomi-

nantly in amorphous regions, we investigated the effects of

the presence of PDLAon proteinaseK-catalyzed enzymatic

degradation of PLLA in an amorphous state.[140] Assuming

that PLLA and PDLA have no interaction with each other,

PLLA in blends with PDLAwill be enzymatically degraded

in the presence of proteinase K as in nonblended PLLA.

However, the enzymatic hydrolysis rate (REH) of PLLAwas

largely reduced by the presence of PDLA (Figure 27). In

otherwords, the presence of PDLAdisturbed the adsorption

or cleavage process of proteinase K. The finding here

reflects the fact that PLLAandPDLAchains arewell-mixed

in the amorphous state and that they have strong interaction

with each other.

7. Applications

7.1. Biodegradable Films

Biodegrdable PLA-based stereocomplex films can be pre-

pared by the solution-casting method with organic solvents

such as chloroform and methylene chloride.[20,62] In this

method, the molecular weights of L-lactyl unit sequences

and D-lactyl unit sequences and the solvent evaporation rate

are crucial parameters. Molecular weights and solvent eva-

poration rate which are too high disturb the stereocomplex

formation, resulting in the formation of films containing a

relatively large amount of homo-crystallites or having low

crystallinities.[20] Although PLA stereocomplex films can

also be prepared by the melt-molding method, it should be

noted that the critical molecular weights for PLLA and

PDLA, below which only stereocomplex crystallites are

formed, decrease dramatically compared with those in the

solution-casting method.[22] This indicates the difficulty in

preparing well-stereocomplexed PLA materials with high

molecular weights.

7.2. Biodegradable Fibers

Murdoch and Loomis[62] prepared melt-spun PLA stereo-

complex fibers from equimolar mixture of PLLA and

PDLA, while Tsuji et al. obtained wet- and dry-spun PLA

stereocomplex fibers[77] from mixed chloroform solutions

of equimolar PLLA and PDLA. In the former study no

estimation of the fractions of stereocomplex crystallites and

Figure 27. Proteinase K-catalyzed enzymatic hydrolysisrate (REH) of blended films from PLLA and PDLA and as afunction of XD.

[140]



homo-crystallites was carried out,[62] whereas in the latter

study fraction estimation byDSC revealed that hot-drawing

of as-spun fibers can increase the amount of stereocomplex

crystallites and reduce that of homo-crystallites, resulting in

the formation of fibers whose main crystalline kind is

stereocomplex.[77] The PLA stereocomplex fibers used by

Tsuji and Suzuki[134] for hydrolysis experiments, which

were prepared by melt-spinning and subsequent two-stage

hot-drawing, contain only stereocomplex crystallites and

no homo-crystallites.

Later, Takasaki et al.[141] revealed that stereocomplexa-

tion is favored in melt-spun fibers from equimolar mixtures

of PLLA and PDLAunder the spinning conditions of higher

take-up velocity, lower throughput rate, and lower extrusion

temperature. This result suggests that these conditions can

enhance the orientation-induced crystallization of the

stereocomplex, as described above.[77,134] They also con-

firmed that drawing at a lower temperature and annealing

between the Tm of stereocomplex crystallites and homo-

crystallites further enhanced stereocomplexation in agree-

mentwith the aforementionedfindings.[22,62]Themaximum

tensile strength and Young’s modulus were respectively

530 MPa and 7.4 GPa for melt-spun and drawn stereo-

complex fibers,[62] 920 MPa and 8.6 GPa for solution-spun

and drawn stereocomplex fibers,[77] and 400 MPa and

4.7 GPa for as-spun stereocomplex fibers.[141] These values

are so far lower than the maximum tensile strength and

Young’s modulus, 1.8 GPa and 14 GPa, of melt-spun and

drawn PLLA fibers.[142]

7.3. Biodegradable Microspheres for DDS

Loomis and Murdoch[65] prepared injectable stereocom-

plex microspheres containing a naltrexone base using the

oil-in-water (O/W) solvent-evaporationmethod (O: methy-

lene chloride, W: water with a surfactant) and the release

rate was determined in various media. The release of

naltrexonewas delayed by a lag time of 200, 230, and 240 h

in water, acid and buffer solutions, respectively. After the

lag the release occurred in zero order up to 450 h with 46,

48, and 35% of the drug released in water, acid and buffer

solutions, respectively. On the other hand, de Jong et al.[102]

prepared stereocomplex hydrogels from dextran (DS¼ 3–

12)-graft-L- and D-lactic acid oligomers (DP¼ 6–12) and

showed that the stereocomplex gels released the entrapped

model proteins (IgG and lysozyme) during six days.

Slager and Domb formulated hetero-stereocomplex

DDS particles from L-configured peptides such as insulin

with PDLA, PDLA-b-PEG, PDLA-b-PEG-PDLA, PLLA/

PDLA, or PLLA-b-PEG/PDLA-b-PEG.[122] The strong

physical entrapment of peptides by the D-lactide unit

sequence resulted in retarded release of the peptides. They

also prepared hetero-stereocomplex DDS particles from an

L-configured leuprolide and PDLA.[119–121] Various factors

affecting the release of leuprolide from the hetero-

stereocomplex particles were investigated. The release rate

of leuprolide from the particles increased with decreasing

the molecular weight of PDLA and increasing the weight

fraction of leuprolide. Continuous release of leuprolide for

over one hundred days was observed for certain stereo-

complex compositions.[121]

7.4. Biodegradable Hydrogels

Stereocomplexed PLA hydrogels can be prepared in

aqueous media by blending block or graft copolymers with

hydrophilic segments and L-lactyl unit sequences or

D-lactyl unit sequences. Stereocomplex hydrogels were

reported for enantiomeric A-B diblock and A-B-A triblock

copolymers of PLA (A) with PEG (B),[95,96] poly[2-

hydroxyethyl methacrylate-graft-oligo(lactide)],[98]

dextran-graft-lactic acid oligomers,[86,99–102] and

pHPMAm-graft-lactic acid oligomers.[103]

On the other hand, Watanabe and Ishihara et al.[104–106]

prepared porous stereocomplexed PLA films from graft-

type copolymers, PMBLLA and PMBDLA, using an ex-

traction procedure with water-soluble particles of NaCl[104]

and investigated the cell adhesion and morphology on the

porous scaffolds.[106] They revealed that the number of

adhering cells is correlated with the PLLA or PDLA con-

tent, and that cell morphology is correlated with the MPC

unit content. Fibroblast cells adhered on the surface and

intruded into the scaffolds through the connected pores after

24 h. The cell morphology became round from spreading

with the decreasing PLLA or PDLA content in the

scaffolds.

7.5. Nucleation Agents

Schmidt and Hillmyer[143] and Yamane and Sasai[144] re-

ported that stereocomplex crystallites formed by the

addition of small amounts of PDLA to PLLA and act as

heterogeneous nucleation sites for PLLA crystallization, or

that PLLA homo-crystallites are formed epitaxially on

the stereocomplex crystallites. Such nucleation agents

increase the number of PLLA spherulites per unit volume

and the total crystallization rate but does not alter spherulite

growth rate G. The nucleation effects must arise from

epitaxial crystallization of PLLA homo-crystallites on the

stereocomplex crystallites, as reported for PLLA and

poly(L-lactide-co-D-lactide) (20/80) when they were mixed

at a ratio of 80/20 and crystallized during slow cooling from

the melt.[68]

8. Conclusions and Perspectives

Stereocomplexation gives PLA-based materials higher

mechanical performance, thermal resistance, hydrolysis-

resistance, and opens a newway to produce various types of

594 H. Tsuji


biodegradable materials such as hydrogels and DDS parti-

cles. The former improvements arise from the peculiarly

strong interaction between L-lactyl unit sequences and

D-lactyl unit sequences. A variety of properties of stereo-

complexed PLAmaterials can bemanipulated bymolecular

characteristics, highly-ordered structures, and additives.

Some Lactobacilli are reported to produce exclusively

D-lactic acid (not the mixture of L- and D-lactic acids) from

numerous kinds of renewable resources,[30,145] and PDLA

can be produced from D-lactic acid by the same procedure

for PLLA production from L-lactic acid. Therefore, the

most crucial issue for stereocomplexed PLA materials,

the reduction of the production cost of PDLA, can be solved

by large-scale facilities. Reduced cost of PDLA will give

stereocomplexed PLA materials further applications, not

only as biomedical materials but also as alternatives for

commercial polymeric materials.

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