Polymer Degradation and Stability 94 (2009) 14191426

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Polymer Degradation and Stability

journal homepage: www.elsevier.com/locate/polydegstab

Rapid controlled hydrolytic degradation of poly(L-lactic acid) by blending

with poly(aspartic acid-co-L-lactide)
Hideko T. Oyama a, *, Yoshikazu Tanaka a, Ayako Kadosaka b
a
b

Department of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
Materials Laboratory, Mitsui Chemicals Inc., 580-32 Nagaura, Sodegaura, Chiba 299-0265, Japan

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 10 April 2009
Received in revised form
5 May 2009
Accepted 11 May 2009
Available online 21 May 2009

Although poly(lactic acid) is known as a biodegradable polymer, its hydrolytic degradation is extremely
slow, taking years in water and in the human body. In this study the effects of blending oligomeric
poly(aspartic acid-co-lactide) (PALs) on the hydrolytic degradation of poly(L-lactic acid) (PLLA) were
studied in detail. It was found that the addition of PAL did not accelerate the hydrolysis of the PLLA in air
(25  C, 60% relative humidity), but signicantly accelerated it in a phosphate buffer solution. The
degradation rate becomes higher for the blends containing PAL with higher molar ratios of lactide to
aspartic acid units, [LA]/[Asp], when PLLA/PAL blends prepared with different PALs are compared at the
same PAL concentration. TEM results, in which the distribution of PALs with higher [LA]/[Asp] occurs at
a smaller scale in blends, imply that higher miscibility of the PAL with PLLA results in higher contact area
between the components, thereby accelerating the degradation efciently.
2009 Elsevier Ltd. All rights reserved.

Keywords:
Poly(L-lactic acid)
Hydrolysis
Aspartic acid
Miscibility

1. Introduction
The most widely used bioresorbable materials in the market,
such as aliphatic polyester poly(L-lactic acid) (PLLA), utilize
hydrolysis of ester linkages for reducing molecular weight [1]. PLLA
is a thermoplastic polymer with high-strength and high-modulus,
and has a higher glass transition temperature (Tg) (ca. 60  C) and
a higher melting temperature (Tm) (ca. 170  C) than other aliphatic
polyesters. Furthermore, it is non-toxic and degradable in vivo as
well as in the environment, albeit slowly, and has good biocompatibility and bioresorption ability. Because of these unique properties it is used for various medical applications such as
bioresorbable scaffolds for tissue regeneration [2], the matrices for
drug delivery systems (DDS) [3], and degradable sutures [4].
PLLA undergoes hydrolysis by a non-enzymatic mechanism in
vivo and in water. Its reaction proceeds through two steps [5]. First,
hydrolysis of the ester linkages located in the main chain occurs in
a random manner, and results in scission of PLLA into smaller
chains. Second, generation of water-soluble monomer and oligomer begins, and this is marked by an onset of weight loss. Finally,
the decomposition products are naturally metabolized to yield

* Corresponding author. Tel./fax: 81 3 3985 2363.

E-mail address: hideko-oyama@rikkyo.ac.jp (H.T. Oyama).
0141-3910/$ see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.polymdegradstab.2009.05.008

carbon dioxide and water. The rst reaction step is very slow so that
it is the rate determining step for the whole hydrolysis process.
The PLLA is inherently hydrophobic so that its degradation is
slow and its hydrolysis rate is difcult to control. It is reported that
the non-enzymatic degradation in water and the human body is so
slow that PLLA materials often remain for years without bioresorption [6,7]. Kinetic data obtained in vitro indicate that PLLA
crystalline residues remain intact for over 5 years [8].
Copolymerization is the most common way to accelerate
hydrolysis and works by changing the chemical structure,
concentration, or arrangement of the comonomer. It is believed
that this occurs because the regularity in the macromolecular
structure decreases by the introduction of comonomers of different
chemical structure, thereby increasing molecular mobility and
facilitating the access of water molecules. For example, various
copolymers (PLGA) of L-lactide (or D, L-lactide)/glycolic acid [9,10],
block copolymers of PLLA with poly(ethylene glycol) [11,12], and
terpolymers of PLLA with poly(oxypropylene) [13] were produced
to increase the hydrolysis rate of PLLA. Excellent reviews on
hydrolytic degradation and biodegradation of PLGA are available
[14,15].
Another promising method to accelerate the hydrolysis is to
introduce a branched structure in the PLLA chain. This suppresses
crystallization and increases the concentration of terminal groups
[16], thus increasing hydrolysis rates. It has been demonstrated that
the hydrolysis rate of poly(lactic acid) is changed by varying

1420

H.T. Oyama et al. / Polymer Degradation and Stability 94 (2009) 14191426

the enantiomeric composition of the poly(lactic acid) [2,1719],

crystallinity and crystalline thickness [7,19,20], molecular weight
[19,21], orientation [22], temperature [23], and terminal end
groups [24]. Usually crystalline PLLA is highly resistant to hydrolysis, but because of its amorphous nature, poly(D, L-lactic acid) is
more sensitive to hydrolysis. However, the hydrolysis of poly(D, Llactic acid) is still slow and its mechanical properties are inferior to
those of crystalline PLLA. Hydrolysis of PLLA is catalyzed by both
acids and bases, so pH affects the hydrolysis rate as well [25,26].
Additives also have effects on hydrolysis rates. For example,
citrate esters [27], mesoporous silica [28], and lauric acid [29]
accelerate the hydrolysis rate, whereas zinc carbonate and calcium
carbonate retard it [30]. Here, the safety of additives is a concern for
some applications. For example, lauric acid is not authorized for use
in internal medical devices as it has an intravenous LD50 in mice of
131 mg kg1.
Although different approaches to accelerate the hydrolysis of
PLLA have been attempted, unfortunately, many of them have
undesired side effects. These include deterioration of mechanical
properties, safety problems with the materials or decomposition
products, loss of transparency, leaching of additives, and difculty
in control of the hydrolytic degradation rate.
Recently poly(aspartic acid-co-L-lactide) (PAL) was newly
synthesized and it was shown that this material is very effective for
acceleration of the PLLA hydrolysis in phosphate buffer saline
solutions, in compost, and in soil environments [31]. An amphiphilic biodegradable PAL is an oligomeric block copolymer with a yshaped architecture, which has three branches of the lactide
segments joined by a succinimide segment at the center [32].
PAL can be prepared from safe raw materials of LA and Asp without
using any catalysts or solvents. It is also found that PAL accelerates
the hydrolysis of other aliphatic polyesters as well, such as
poly(butylene succinate) (PBS) and poly(3-caprolactone) (PCL).
Furthermore, the analysis of the PLLA/PAL blend lm by infrared
spectroscopy by the attenuated total reectance (ATR) method
conrmed that after the immersion of the lm in water the ring of
the succinimide group of PAL is opened, converting it to the aspartic
acid form, as shown in Fig. 1 [32].
Importantly, it was found in a previous study that PLLA has poor
compatibility with polysuccinimide (PSI) prepared by thermal
polycondensation of L-aspartic acid, whereas PLLA has good
compatibility with PAL due to the presence of lactide segments in
the PAL copolymer [31]. This poor compatibility resulted in

CH3
O

O CH C OH
q

CH3

H
H O C C N
p
H
O

CH3
n

2. Experimental
2.1. Materials
Poly(L-lactic acid) (PLLA) manufactured by Mitsui Chemicals Inc.
(Tokyo, Japan), Lacea(H400), was used in the present study. It
is reported that it contains ca. 12% of D-lactide with the rest being
L-lactide. Four kinds of poly(aspartic acid-co-L-lactide) (PAL)
copolymers with different molar ratios of L-lactide (LA) to aspartic
acid (Asp) units, PAL5, PAL20, PAL30, and PAL50, were supplied by
Mitsui Chemicals Inc. The numbers at the end of the abbreviations
represent the [LA]/[Asp] molar ratios. The detailed procedures for
the synthesis of PAL are described elsewhere [32]. Characterization
results of the PLLA and PALs used in the present study are
summarized in Table 1. The results indicate that PALs are amorphous oligomers with number-average molecular weights (Mn) in
the range of 1.0 4.3  103 (g/mol). The average unit sequence
lengths of Asp and LA in various PALs are estimated to be 2.3 and
3.9 units for PAL5, 1.8 and 11.9 units for PAL20, 1.8 and 18.4 units for
PAL30, and 1.2 and 19.5 units for PAL50, respectively.
2.2. Melt-mixing and compression-molded lm formation
PLLA and PAL were melt-mixed at 200  C for 5 min with
a rotation speed of 50 rpm in a twin blade mixer consisting of
a motor and controller (Toyo Seiki, Labo Plastomill 4M150, manufactured in Japan) attached to a mixer (Toyo Seiki, KF70V2). The
resultant blends were rst hot-pressed at 190  C and then coldpressed at 0  C to prepare lms with ca. 500 mm thickness. The lms
were used for various analyses.
2.3. Degradation tests
Four lm specimens with dimensions of 90 mm  45
mm  0.5 mm were placed in a 200 ml glass vial lled with
a phosphate-buffered saline solution (pH 7.3), which was
immersed in a water bath held at 40  C. The specimens were
hydrolyzed for 0 120 days and were then withdrawn from the test
environment, washed with de-ionized water, dried in vacuo, and

O CH C OH
r

deterioration in mechanical properties and loss of transparency.

Therefore, in this study the blend lms were prepared using PALs
with different molar ratios of the lactide unit (LA) to the aspartic
acid unit (Asp) in order to study effects of the PAL composition on
the blend structure and the kinetics of hydrolysis. The hydrolytic
degradation of PLLA/PAL in phosphate-buffered solution was
investigated using gel permeation chromatography (GPC), transmission electron microscopy (TEM), x-ray diffraction (XRD), and
differential scanning calorimetry (DSC).

Table 1
Characterization of PLLA and PALs.
Molecular weight

H2O

Mn (g/mol)

CH3
O CH C OH
q

O
CH3

O
NH

CH3

H
H O C C N
p
H
O

O
OH

O CH C OH
O

Fig. 1. Change in the chemical structure of PAL by hydrolysis.

PLLA
PAL5
PAL20
PAL30
PAL50

1.3
1.0
2.7
4.1
4.3







105
103
103
103
103

Thermal properties

Mw (g/mol)
2.0
4.7
6.0
9.3
8.2







105
103
103
103
103

Mw/Mn

Tg ( C)

Tm ( C)

1.54
4.70
2.22
2.27
1.91

58
55
55
54
49

168

a
The number-average (Mn) and the weight-average (Mw) molecular weights of
each sample were measured by GPC using chloroform as eluent and monodispersed
polystyrenes as standards.
b
Polymer samples were heated at a rate of 10  C/min in a N2 atmosphere. Glass
transition temperature (Tg) and melting point (Tm) were detemined from the heat
ow curves.

H.T. Oyama et al. / Polymer Degradation and Stability 94 (2009) 14191426

1421

used for various analyses. To study hydrolysis in air the lm specimens were placed for 120 days under an atmosphere adjusted to
25  C and 60% relative humidity (RH). The change in molecular
weight of these specimens was investigated by gel permeation
chromatography (GPC) using a setup consisting of a liquid chromatograph pump (JASCO PU-2080 Plus manufactured in Japan),
a column (Tosoh TSK gel GMHxL manufactured in Japan) and
a differential refractometer (JASCO RI-2031 Plus). Chloroform was
used as eluent at a ow rate of 1.0 ml/min at 40  C. The molecular
weight was calibrated using monodisperse polystyrene standards.
For each data point, the same experiment was repeated at least
three times in all systems.
2.4. Transmission electron microscopy (TEM)
The samples exposed to ruthenium tetraoxide (RuO4) vapor
were microtomed at room temperature prior to TEM measurements. The transmission electron microscope (Phillips Tecnai 30),
with a high angle annular dark-eld detector (TEMHAADF) was
used with an acceleration voltage of 300 kV. It is highly sensitive to
variations in the atomic number of atoms in the sample, with the
regions containing elements with high electron density appearing
in light color. Therefore, in the TEMHAADF micrographs of the
present experiments, the area predominantly stained by RuO4
appears in light color.
2.5. Thermal analysis
Glass transition temperature (Tg), melting temperature (Tm), and
crystallinity (Xc) of specimens were estimated under a nitrogen
atmosphere with a differential scanning calorimeter (TA Instruments, DSC-Q200, manufactured in USA) at a heating rate of 10  C/
min. Based on these DSC data, the crystallinity (Xc) of each specimen was estimated from the following equation:

Xc % 100DHm  DHc  DHr =DHf

(1)

where DHm, DHc, and DHr are respectively the enthalpies of

melting, cold crystallization, and rearrangement of polymer chains.
Here, the value of DHf, the heat of fusion, dened as the melting
enthalpy of 100% crystalline poly(lactic acid), was taken to be 93 J/g
from the literature [33].

Fig. 2. . Change in appearance of (a) neat PLLA and (b) (80/20) PLLA/PAL5 blend during
hydrolytic degradation.

fragments at the same period of immersion time. The color of the

neat PLLA lm and the (80/20) PLLA/PAL5 lm turned from transparent to white after 120 days and 30 days of immersion time,
respectively.
Furthermore, Fig. 3 indicates the change in remaining mass of
the specimens in the course of the hydrolysis. It shows that the
weight loss became more signicant with increase of the PAL
concentration and the immersion time: at 100 days of immersion
the weight loss was almost negligible in the neat PLLA lm,
whereas it was as high as ca. 15 wt% and 20 wt% in (90/10) and (80/
20) PLLA/PAL5 blends, respectively. The weight loss of the specimens indicates that the hydrolysis proceeded into the second step,
in which PLLA and/or PAL were degraded down to oligomers or
monomers soluble in water [5].

2.6. X-ray diffraction (XRD)

100

3. Results and discussion

3.1. Change in appearance and weight of PLLA/PAL blend lms
during hydrolytic degradation
PLLA/PAL blends were prepared by melt-mixing using compositions with weight ratio of 97/3, 95/5, 90/10, and 80/20 by using
different kinds of PAL. Then, hydrolysis experiments were carried
out by immersing lm specimens of the so-obtained blends and the
neat PLLA in a phosphate buffer saline solution controlled at 40  C
for given time intervals. Fig. 2 shows the change in appearance of
the neat PLLA and (80/20) PLLA/PAL5 blends during hydrolytic
degradation, and indicates that the addition of PAL signicantly
facilitates the hydrolysis of PLLA. The neat PLLA lm retained its
shape even after 120 days of immersion, whereas the (80/20) PLLA/
PAL5 blend lm was swiftly degraded and collapsed into small

Remaining Mass (%)

XRD patterns (Cu Ka1 line, 40 kV, 50 mA) were obtained at

a scanning speed of 2 /min using an x-ray diffractometer (Rigaku,
Ultrax 18SF, manufactured in Japan).
95

90

85

80
0

20

40

60

80

100

Time (days)
Fig. 3. Remaining mass of neat PLLA and [(100-X)/X] PLLA/PAL5 blends during
immersion in a phosphate buffer saline solution. [-: X 0, C: X 3, :: X 5, ;:
X 10, A: X 20 ].

1422

H.T. Oyama et al. / Polymer Degradation and Stability 94 (2009) 14191426

140

120

Mn of PLLA x 10-3 (g/mol)

Mn of PLLA x 10-3 (g/mol)

120

140

100
80
60
40
20

100
80
60
40
20
0

0
0

20

40

60

80

100

120

20

Time (days)

60

80

100

120

100

120

Time (days)

140

Mn of PLLA x 10-3 (g/mol)

120

Mn of PLLA x 10-3 (g/mol)

40

100
80
60
40
20

140
120
100
80
60
40
20

0
0

20

40

60

80

100

120

Time (days)

20

40

60

80

Time (days)

Fig. 4. Change in number-average molecular weight (Mn) of neat PLLA and [(100-X)/X] PLLA/PAL blends during immersion in a phosphate buffer saline (solid lines) and exposure to
air (dotted lines) for (a) PLLA/PAL5, (b) PLLA/PAL20, (c) PLLA/PAL30, and (d) PLLA/PAL50, respectively. [-: X 0, C: X 3, :: X 5, ;: X 10, A: X 20 ].

3.2. Gel permeation chromatography (GPC)

Next the degradation of the PLLA/PAL blends in the phosphate
buffer saline solution was further examined using gel permeation
chromatography (GPC) analysis. Fig. 4(a) indicates the change in
number-average molecular weight (Mn) of PLLA/PAL5 at compositions from (100/0) to (80/20) by weight ratio, when the blend lms
were placed either in air (dotted lines with open marks) or in
a buffer saline solution (solid lines with solid marks) for given
times. The initial decrease in Mn before the degradation tests
observed for PLLA/PAL5 is due to the contribution of added oligomeric PAL and/or due to degradation of PLLA proceeding to some
extent during melt-blending for preparation of the blends. The
results in Fig. 4(a) clearly demonstrate that under an air atmosphere controlled at 25  C and 60% RH the addition of PAL5 did not
accelerate degradation, with the slope of the Mn change in the
PLLA/PAL5 blends showing the same value as the neat PLLA. This is
probably because (i) the hydrophobic PLLA matrix suppresses
access of water molecules to PAL in air and (ii) the aspartic acid unit
of PAL transforms to its dehydrated form, i.e. a succinimide group,
with hydrophobic properties in the dry solid, as shown in Fig. 1 [32].
Thus, this result indicates that the PLLA/PAL blends are hardly
degraded during handling or storage in air.
In contrast, when the PLLA/PAL blends were placed in a buffer
saline solution at 40  C the hydrolysis was dramatically accelerated

with increase of the PAL concentration. After 120 days of immersion, the Mn of the PLLA in (80/20) PLLA/PAL5 dropped to
2300 g/mol, whereas that of the neat PLLA stayed as high as
71,000 g/mol. This indicates that when the PLLA/PAL is immersed in
water, hydrolytic degradation is suddenly switched on. This reaction is attributed to the high hydrophilicity of PALs containing
aspartic acid units and the terminal carboxylic acid groups. As
indicated in Fig. 1, opening of the succinimide ring forms aspartic
acid functionalities, and the resultant carboxylic acids can carry out
acid catalysis, thereby hydrolyzing the ester linkage of PLLA efciently [32].
The miscibility between PLLA and PAL is expected to change by
the PAL composition, which might also affect the hydrolytic
degradation process. To check this point blend lms were prepared
using PALs with different molar ratios of the lactide unit (LA) to the
aspartic acid unit (Asp). Changes in Mn upon hydrolysis of the PLLA/
PAL20, PLLA/PAL30, and PLLA/PAL50 blends containing different
PAL concentrations are summarized in Fig. 4(b)(d), respectively. As
shown in Fig. 4(a), the hydrolytic degradation further progresses
with the growth of the PAL concentration and the immersion time
in all systems.
Fig. 5 shows the change in the molecular weight (M) distribution
during hydrolytic degradation for PLLA, (95/5) PLLA/PAL5, and (80/
20) PLLA/PAL50, respectively. It was found that the GPC spectra
show one broad peak in each system, with the blends in which

H.T. Oyama et al. / Polymer Degradation and Stability 94 (2009) 14191426

1423

50

PLLA

kPLLA x 103 (day-1)

Intensity

40

PLLA/PAL5

PLLA/PAL50

30

20

10

2.8

3.2

3.6

4.0

4.4

4.8

5.2

5.6

6.0

log M

0.0

0.5

3.3. Kinetics analysis of hydrolytic degradation

The degradation kinetics of the PLLA/PAL blends prepared with
different PALs at various concentrations were investigated using
data on their Mn values after 060 days of immersion. It was found
that the hydrolytic degradation in all PLLA/PAL systems was well
described with rst-order kinetics, as reported in the literature on
degradation of neat PLLA [18,3436]. The hydrolytic degradation of
PLLA is known to proceed via a self- or autocatalytic process
involving its terminal carboxylic acid groups, whose concentration
increases by hydrolysis [18,24].
Fig. 6(a) summarizes kinetic data for all blends prepared with
different kinds of PAL at different concentrations, in which the
degradation rate constants (k) of PLLA are plotted against the mole
concentration of PAL ([PAL]) in the unit mass of each blend. It is
shown that the degradation rate constants increase linearly with
the growth in [PAL], which clearly demonstrates PAL is an effective
accelerator for the hydrolysis of PLLA. Furthermore, Fig. 6(a)
enables us to understand the effects of the PAL composition on the
degradation rate, since at the same x value the blends prepared

1.5

2.0

40
PAL30

30

kPLLA x 103 (day-1)

more degradation occur tending to have a broader distribution

compared to the neat PLLA. The monotonous shift of the single GPC
peak toward lower molecular weight observed in the two PLLA/PAL
blends indicates random scission of the ester bonds in PLLA/PAL
blends, in the same manner as in the neat PLLA [20]. By contrast, it
is reported that in the degradation of initially crystallized PLLA,
multiple GPC peaks appear with the progress of hydrolysis due to
different degradation rates in the amorphous and crystalline
regions [20].
Thus, the present results indicate that PAL has very high
potential as degradation accelerator. First, it does not induce
degradation in air, but when immersed in water, it turns on
a degradation pathway. So far the acceleration of PLLA hydrolysis
often has been achieved by adding hydrophilic comonomers or
additives. The addition of hydrophilic structures or materials causes
hydrolysis of PLLA in air by moisture uptake, which makes control
of mechanical properties impossible. So it is a big advantage that
degradation is not induced in air as conrmed in the present PLLA/
PAL system. Second, PAL can be prepared from safe raw materials of
LA and Asp without using any catalysts or solvents, so this is
a signicant advantage for medical applications [32]. The degradation products are also considered to be totally non-toxic to the
environment and the human body.

1.0

[PAL] in the blend x 104 (mol/g)

Fig. 5. GPC spectra of PLLA, (95/5) PLLA/PAL5, and (80/20) PLLA/PAL50 after hydrolysis
0 day, :
30 days, :
100 days].
for different times. [:

PAL50
PLLA/PAL
PAL20
20

10

PAL5
PLLA

0
0.00

0.05

0.10

0.15

0.20

[Asp] in PAL (molar fraction)

Fig. 6. (a) Hydrolysis rate constants (k) of PLLA in the absence of PAL or in the presence
of PAL at different concentrations in a phosphate buffer saline solution at 40  C. [-:
PAL5, B: PAL20, :: PAL30, 7: PAL50], (b) Hydrolysis rate constants (kPLLA) of PLLA at
5.0  105 mol/g PAL concentration in the blend vs. molar fraction of the aspartic acid
units in PAL used for blend preparation.

with different PALs contain an identical number of terminal

carboxyl groups originated from the PAL molecule, which are
expected to function as acid catalysis for the hydrolysis. The slope in
Fig. 6(a) tends to increase for the blends containing PAL with higher
[LA]/[Asp] ratios.
Then, in order to clarify this point, the rate constants at the same
[PAL], say 5.0  105 mol/g, were compared between blends
prepared with various PALs. So-obtained k values for different
blends were plotted against the PAL composition in Fig. 6(b). It is
shown that the rate constant tends to increase as a decrease in
[Asp] of the PAL. This means that the degradation rate becomes
faster for the blends containing PAL with higher [LA]/[Asp], when
PLLA/PAL blends prepared with different PALs are compared at the
same PAL molar concentration. For example, the hydrolysis of
the blend prepared with PAL50 was ca. 3 times faster than that of
the blend prepared with PAL5. Moreover, PAL50 increases the
hydrolysis rate of the neat PLLA by ca. 8 times at 5.0  105 mol/g of
[PAL] in the blend.
It is already recognized that addition of hydrophilic polymers to
PLLA is effective for the acceleration of the non-enzymatic and
enzymatic degradation of PLLA, such as poly(ethylene glycol) (PEG)

1424

H.T. Oyama et al. / Polymer Degradation and Stability 94 (2009) 14191426

Fig. 7. TEMHAADF micrographs of two PLLA/PAL blends containing the same [Asp] in the blends (stained by RuO4). [(a) (95/5) PLLA/PAL5 and (b) (80/20) PLLA/PAL20].

3.4. Structure of PLLA/PAL

Fig. 7(a) and (b) show TEMHAADF micrographs of the (95/5)
PLLA/PAL5 and (80/20) PLLA/PAL20 blends, respectively, in which
the total concentration of the aspartic acid unit is the same in the
two blends. The PLLA/PAL5 blend displays macrophase separation
with the formation of a dispersed phase of 150 nm size. On the
other hand the PLLA/PAL20 blend does not show the presence of
a dispersed phase despite the addition of a larger amount of PAL.
There are two possible explanations for these results. The rst
possibility would be a miscibility enhancement between PLLA and
PAL with decrease in the molar fraction of the aspartic acid units
and an increase in the molar fraction of the lactide units of PAL.
Usually different polymers are thermodynamically immiscible.
However, the PAL used in the present work is an oligomer so that
the PLLA/PAL blend could be considered similar to a polymer/
solvent system, in which the combinatorial entropy term would
contribute to a decrease in free energy of mixing in the Flory
Huggins relationship [39]. If so, miscibility might be induced
between PLLA and PAL, especially in the case of PAL with the higher
[LA]/[Asp] ratios.
The second possibility would be solubilization of PLLA chains
into the lactide segments of PAL. In this case, PLLA and PAL would
not be homogeneously and randomly mixed at a molecular level
like a miscible system, but nevertheless the PLLA and PAL would be
mixed reasonably well so that the scale of the distributed PAL might
become too small to be observed at the magnication of Fig. 7(b).
Whichever the case may be, the higher distribution of PAL is achieved in the blends containing PAL with the higher [LA]/[Asp] ratios,

therefore a higher contact area of PAL with PLLA would result in

a faster degradation in these samples.
The results in the degradation tests of two blends shown in
Fig. 7(a) and (b) indicated that (80/20) PLLA/PAL20 is degraded
faster than (95/5) PLLA/PAL5, although both blends contain the
same concentration of the aspartic acid unit. This might be due to
the higher concentration of the terminal carboxylic acid group of
PAL and the higher distribution of PAL in the former blend than in
the latter blend. Furthermore, the scanning electron microscopy
measurements conrmed that after hydrolytic degradation the
surface of (95/5) PLLA/PAL5 has lots of pores left, whereas that of
(80/20) PLLA/PAL20 is very smooth. This result indicates that the
hydrolytic degradation initiates from the phase-separated domains
in (95/5) PLLA/PAL5, however, it proceeds more homogeneously in
(80/20) PLLA/PAL20.
3.5. Changes in crystallinity during hydrolytic degradation
Fig. 8 shows typical DSC thermograms of the neat PLLA and the
(95/5) PLLA/PAL5 blend before and after the degradation experiments performed for 100 days. The endothermic changes appeared
PLLA

Exthotherm

[37] and poly(vinyl alcohol) (PVA)[38]. In PLLA/PVA blend lms the

enhanced non-enzymatic hydrolysis of PLLA is ascribed to
the increased water concentration around PLLA molecules and the
water supply rate to them by the presence of hydrophilic PVA both
in PLLA-rich and in PVA-rich phases. In the phosphate-buffered
solution held at 37  C, the rate constant (k) of the PLLA hydrolysis
for 012 months was enhanced 1.9 times and 2.1 times by addition
of 20 wt% and 40 wt% of PVA, respectively. These results clearly
indicate that PAL used in the present study is much more effective
as a degradation accelerator compared to hydrophilic polymer, PVA.
It is also reported that addition of 4.5 wt% of lauric acid to PLLA
accelerates hydrolytic degradation of PLLA to 3  102 day1 in pH
7.4 phosphate-buffered solution at 37  C, which corresponds to
a degradation rate ca. 510 times faster than that of pure PLLA
reported in the literature [29]. So the present results show that the
efcacy of PAL at 5.0  105 mol/g of [PAL] in the blend is similar to
that of 4.5 wt% lauric acid.

PLLA/PAL5

40

60

80

100

120

140

160

180

Temperature (C)
Fig. 8. Differential scanning calorimetry (DSC) thermograms of PLLA and (95/5) PLLA/
PAL5 before (solid line) and after (broken line) hydrolysis for 100 days.

H.T. Oyama et al. / Polymer Degradation and Stability 94 (2009) 14191426

a 60

Crystallinity (%)

50

40

30

20

10

0
0

20

40

60

80

100

120

Time (days)

b 60
50

Crystallinity (%)

at ca. 60  C for the glass transition temperature (Tg) and at 150

170  C for the melting temprature (Tm). The DSC thermograms also
show two exothermic peaks due to crystallization: one is assigned
to cold crystallization (Tc) observed at ca. 100  C and the other is
assigned to rearrangement crystallization (Tr) observed at ca.
150  C, just before an endothermic phenomenon occurrs due to
melting of the crystallites. Changes in Tg, Tm, and crystallinity (Xc)
during the degradation process are plotted in Fig. 9(a) and (b). Here
PAL is an amorphous material so that the DHm, DHc, and DHr values
obtained from the peak areas at Tg, Tm, and Tr, are respectively
ascribed solely to PLLA. The Xc was calculated by Eq. (1). In the
blend a signicant decrease in Tm by 12  C was accompanied by
a considerable increase in Xc at 100 days of immersion time, in
which the Tg peak in the DSC thermogram of the blend became
invisible due to the high crystallinity. In this study a signicant
decrease in Tm was not observed in the degradation of the neat PLLA,
however, the decrease has been reported in the literature when the
hydrolytic degradation proceedes for over 12 months [35].
A change in Xc for the PLLA/PAL5 samples with different
compositions is plotted against the immersion time and the
number-average molecular weight (Mn) in Fig. 10(a) and (b),
respectively. It is indicated in Fig. 10(a) that in the blends with
increase in the immersion time and the concentration of PAL, the
crystallinity is dramatically enhanced, whereas in the neat PLLA it
increases only slightly.
In Fig. 10(b) the Mn value decreased from 1.30  105 g/mol for
the unhydrolyzed PLLA. It is interesting to note that crystallization
was abruptly promoted, once Mn dropped to ca. 50,000 g/mol. In
any PLLA/PAL blends containing 320 wt% of PAL5, the crystallinity
of PLLA increased to as high as over 50%. In a study on long-term
hydrolysis of initially amorphous neat PLLA, the highest reported Xc
values of the decomposition products are 29% (in vitro at 36
months) [35], 49% (in vitro at 21 months) [40], 60% (in vitro at 26
months) [41], and 84% (in vivo at 52 months) [20].

1425

40

30
20

degradation

10

0
140

120

100

80

60

40

20

Mn of PLLA x 10-3 (g/mol)

60

a 170
Tm

50

160
40
155
30

Tg
65

20

60
55

Crystallinity (%)

Temperature ( C)

165

Fig. 10. (a) Change in crystallinity of PLLA and [(100-X)/X] PLLA/PAL5 blends during
immersion in a phosphate buffer solution. [-: X 0, B: X 3, :: X 5, 7: X 10, A:
X 20], (b) Relationship between number-average molecular weight (Mn) and crystallinity in the neat PLLA and [(100-X)/X] PLLA/PAL5. [-, B, :, 7, A same for
Fig. 10(a) ].

10

Xc

50
0
50

Tm

160

40

155
30

Tg
60

20

55

Xc

Crystallinity (%)

Temperature ( C)

165

10

Intensity

170

(b)

(a)

50
0

20

40

60

80

0
100

Time (days)
Fig. 9. Change in glass transition temperature (Tg), melting temperature (Tm), and
crystallinity (Xc) of (a) PLLA and (b) (95/5) PLLA/PAL5 blend during immersion in
a phosphate buffer solution.

10

20

30

40

50

2 (degree)
Fig. 11. X-ray diffraction proles of (80/20) PLLA/PAL5 (a) before and (b) after
immersion in a phosphate buffer solution for 30 days.

1426

H.T. Oyama et al. / Polymer Degradation and Stability 94 (2009) 14191426

The crystallization induced by the hydrolytic degradation is also

conrmed by XRD measurements of the (80/20) PLLA/PAL5 specimen (with Mn and Mw of 21,000 g/mol and 32,000 g/mol,
respectively) immersed for 30 days, as shown in Fig. 11. The results
show that the initial blend was amorphous, but that upon hydrolytic degradation it formed typical a crystallites.
The same phenomenon of increase in crystallinity upon
hydrolytic degradation was also observed in PLLA mixed with
4.5 wt% lauric acid [29]. It was found that the water-uptake
increased as the degradation proceeded, with the water-uptake
changes being in the range of 13 wt% during 080 days of
degradation time. Combined with results of water-uptake, GPC, and
XRD measurements, it was concluded that chain scission increased
the concentration of hydrophilic chain ends, which resulted in
plasticization of PLLA by absorbed water molecules thereby facilitating the chain mobility and the formation of new crystallites.
In summary, these results demonstrate that the addition of PAL
does not accelerate the hydrolysis of PLLA in air, but signicantly
accelerates it in water. The hydrolysis rate of PLLA can be controlled
by the concentration and the composition (i.e., [LA]/[Asp] ratio) of
added PAL. Thus, the present work demonstrates the high potential
of the PLLA/PAL system for various kinds of materials ranging from
environmentally friendly substances such as water-disposable
substances and medical devices such as tissue scaffolds, and drug
delivery system (DDS), in which control and/or acceleration of the
hydrolytic degradation is necessary. Since PLLA hydrolysis in the
phosphate-buffered solution is reported to be similar to that in
vivo, the present results would be especially valuable for medical
applications [6,42].
4. Conclusions
The present work on hydrolytic degradation of blends
composed of poly(L-lactic acid) (PLLA) and oligomeric poly(aspartic
acid-co-lactide)(PAL) in a phosphate buffer saline solution allows
several important points to be made:
(1) The addition of PAL did not accelerate the hydrolysis of the
PLLA in air (25  C, 60% RH).
(2) The degradation of PLLA was signicantly accelerated by the
addition of PAL in water, with the degradation rate constant (k)
increasing linearly with increase in the PAL concentration,
when the same PAL was used for the blend preparation.
(3) The degradation rate becomes faster for the blends containing
PAL with higher [LA]/[Asp] ratios, when PLLA/PAL blends
prepared with different PALs are compared at the same mole
concentration of PAL. In this comparison a contribution of the
terminal carboxylic acid group in PAL to hydrolysis could be
considered to be the same.
(4) The distribution of PALs with higher [LA]/[Asp] ratios occurs at
a smaller scale in blends, so that the higher contact area of PAL
with PLLA results in a swift degradation. The higher distribution of PAL is probably achieved either by miscibility between
PAL and PLLA or by solubilization of PLLA chains into the lactide
segments of PAL.
(5) The present work demonstrated that non-toxic biomaterials
can be successfully generated, which hardly degrade during

handling or storage in air, but do easily disintegrate in water

forming harmless decomposition products.

Acknowledgment
The authors would like to deeply thank to Shigenari Shida for
the TEM measurements. Financial support was kindly provided by
Mitsui Chemicals Inc.

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