J Polym Environ (2013) 21:1064–1071
DOI 10.1007/s10924-013-0587-x
ORIGINAL PAPER
Poly(Lactic Acid)-co-Aspartic Acid Copolymers: Possible
Utilization in Drug Delivery Systems
Nita Tudorachi • Rodica Lipsa •
Cornelia Vasile • Fanica Mustata
Published online: 7 June 2013
Ó Springer Science+Business Media New York 2013
Abstract The synthesis and characterization of poly(lactic
acid)-co-aspartic acid copolymers (PLA-co-Asp) were pre-
sented. Subsequently, the synthesized PLA-co-Asp copoly-
mers were tested as biodegradable carriers in drug delivery
systems. PLA-co-Asp copolymers were synthesized by
solution polycondensation procedure, using different molar
ratios PLA/L-aspartic acid (2.33/1, 1/1, 1/2.33), manganese
acetate and phosphoric acid as catalysts and N,N0 -dimethyl
formamide (DMF)/toluene as solvent mixture. The copoly-
mers were characterized by FT-IR and 1H-NMR spectros-
copy, gel permeation chromatography (GPC), DSC and
TG-DTG analyses. Diclofenac sodium, a non steroidal
anti-inflammatory drug was subsequently loaded into PLA-
co-Asp copolymers. The in vitro drug release experiments
were done by dialysis of the copolymer/drug systems, in
phosphate buffer solution (pH = 7.4, at 37 °C) and moni-
tored by UV spectroscopy.
Keywords Poly(lactic acid)-co-aspartic acid 
Biodegradable copolymers  Drug delivery systems 
Diclofenac sodium
Introduction
Poly(lactic acid) (PLA) and lactic acid derivatives as
copolymers are much studied in pharmaceutics as drug
delivery systems (DDS), due to their good biodegradabil-
ity, biocompatibility, non-toxicity. PLA is derived from
100 % renewable resources (corn, potato, sugar cane, sugar
N. Tudorachi (&)  R. Lipsa  C. Vasile  F. Mustata
‘‘Petru Poni’’ Institute of Macromolecular Chemistry,
41A Gr. Ghica Voda Alley, 700487 Iasi, Romania
e-mail: tudorachinita@yahoo.com
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beat), degrades hydrolytically, being bioresorbed in the
organism [1]. In recent years in situ implants were for-
mulated, containing doxycicline hydrochloride and/or
secnidazole, that could be used in the treatment of peri-
odontitis by direct periodontal intrapocket administration;
the in situ implants were formulated using PLA and
poly(lactide-co-glycolide) (PLGA), each polymer in two
concentrations: 25 and 35 % w/w, respectively. PLA
implants demonstrated a slower drug release rate than
PLGA; implants composed of 25 % PLGA showed the
fastest drug release [2].
In controlled drug delivery systems poly(D,L-lactic acid)
or poly(D,L-lactide) (PDLLA) are utilized to release drugs
such as: antibiotics, antineoplasic agents, hormones, con-
traceptives. These polymers as matrices enhance the ther-
apeutic effect of the drugs, lower their secondary effects
when are directed to ‘‘target’’ organs. The time required for
complete degradation is dependent on their molecular
structure, morphology, average molecular weight, size and
shape. PLA demonstrated a very good biocompatibility in
parenteral administration and the drug release was only
slightly affected by the molecular weight [3]. To date, PLA
market is limited because of the relatively high cost and
hydrophobicity, brittleness and poor processability, thermal
instability and low melt strength, lack of functional groups,
being critical for the manufacture of useful packaging
products, in DDS and tissue engineering [4]. Also, the de-
gradability of PLA is too low comparative to other biode-
gradable plastics: poly(e-caprolactone) (PCL), poly(3-
hydroxybutyrate) (PHB), poly(butylenesuccinate) (PBS),
polyaspartic acid (PAs); other disadvantages are the accu-
mulation of lactic acid resulted in the process of PLA
degradation, absence of suitable functional groups for
coupling with bioactive agents [5, 6]. Biomedical applica-
tions, such as drug delivery systems or tissue engineering
J Polym Environ (2013) 21:1064–1071
require materials with a certain balance of hydrophobicity/
hydrophilicity (to improve the affinity with various kinds of
drugs or tissues), non-toxicity, effective functionality, per-
formance and durability [7]. In order to modify the hydro-
phobicity and improve biodegradability, physico-chemical
and mechanical properties of PLA, researchers focused on
PLA chemical modification. By copolymerization of lactide
with monomers or polymers such as: malic acid, polyeth-
ylene glycol (PEG), poly(glycolic acid) (PGA) or dextran as
well as blending polylactide with natural derivatives, the
degradation rate, hydrophilicity, mechanical and surface
properties of PLA could be improved [8]. A hydrophilic
biodegradable polymer is polyaspartic acid. It is soluble in
water and degrades quickly under physiological or biolog-
ical conditions. Poly(aspartic acid) (PAs) is generally syn-
thesized by thermal polycondensation of L-aspartic acid,
optionally in the presence of an acid catalyst to obtain
polysuccinimide (PSI), and then by alkali-hydrolysis of PSI
of PAs metal salt is obtained [9]. Ecotoxicity studies have
shown that polyaspartate is a ‘‘green alternative’’ to several
materials and does not adversely impact the environment
[10], whereas other materials that are presently used for the
same purposes are either slowly biodegradable (e.g. poly-
acrylic acid), or harmful to the environment (e.g. poly-
phosphoric acid). PAs is hydrophilic, insoluble in organic
solvents, being processed only as an aqueous solution or in a
hygroscopic powder form.
The paper present the synthesis and characterization of a
novel type of amphiphilic biodegradable copolymer using
PLA (Mn = 2,000) and Asp in different PLA/Asp molar
ratios, manganese acetate and phosphoric acid as catalysts.
Also, the study focused on the preparation of PLA-co-Asp/
diclofenac sodium systems and in vitro drug release in
phosphate buffer solution pH = 7.4, at 37 °C.
Experimental
Materials
L-aspartic acid (98 %) was purchased from Merck, man-
ganese acetate and phosphoric acid from Sigma Aldrich.
L(?)-lactic acid (LA), 90 wt% aqueous solution, density
1.20 g mL-1, was supplied from Fluka (Switzerland) and
used without further purification. Toluene from Chimopar
S.A. (Romania), dimethylformamide (Sigma Aldrich Che-
mie) as analytical grade reagents, were used as received.
Synthesis of Poly(Lactic Acid)
PLA synthesis was carried out by melt polycondensation of
L(?)-lacticacid (174 g, 1.93 mol), in the presence of
1065
manganese acetate as catalyst, (0.40 wt% reported to lactic
acid), in a 250 mL three-neck glass flask equipped with
mechanical stirrer, nitrogen purge, and controlled heating
(contact thermometer). The reaction took place under
nitrogen flow and secondary reaction products (water,
lactide) were removed by a Dean-Stark distillation appa-
ratus. The temperature of the reaction was maintained at
104–110 °C (2.5 h), 140–150 °C (3 h) and 175–180 °C
(1 h). The reaction product presented raised viscosity and
the yield of reaction was 76 %.
Synthesis of Poly(Lactic Acid)-co-Aspartic
Acid Copolymers
Poly(lactic acid)-co-aspartic acid copolymers were syn-
thesized by solution polycondensation procedure, using
different PLA/Asp molar ratios (2.33/1, 1/1, 1/2.33), N,N0 -
dimethyl formamide/toluene as solvent mixture, manga-
nese acetate and phosphoric acid as catalysts. Poly(lactic
acid) (Mn = 2,000) was dissolved in DMF/toluene mixture
(1/1) under stirring at room temperature, a 16 wt% solution
was obtained. The required quantity of Asp was dispersed
separately in the solvent mixture and was subsequently
introduced in the PLA solution. Then, the catalyst (man-
ganese acetate 0.8 wt%, reported to the reaction compo-
nents), dissolved in DMF was added. The reaction took
place in two stages: in the first stage the mixture was
maintained 5 h at 95 °C with reflux, then phosphoric acid
85 wt% aqueous solution (15 wt% reported to the reaction
components) was introduced under continuous stirring in
the reaction vessel. Subsequently, the temperature was
raised at 125–130 °C to collect the secondary reaction
products (water, lactide) and DMF/toluene mixture, using
the equipment of distillation-collection (Dean-Stark trap).
The obtained copolymers were lyophilized at -40 °C
under vacuum of 2 torr, subsequently vacuum dried at
55–60 °C, 48 h for total solvent removal, and finally were
ground. Scheme 1 illustrates the possible reaction pathway
of polylactic acid with aspartic acid, according to literature
data [7, 11]. Phosphoric acid was chosen as catalyst and
manganese acetate co-catalyst in this reaction, as they were
efficient in the synthesis of polylactic acid and other lactic
acid copolymers [12, 13].
Synthesis of Drug Delivery Systems
Diclofenac sodium, [2-(2,6-dichlorophenyl)-amino] ben-
zene acetic acid monosodium salt is a nonsteroidal anti-
inflammatory drug, analgesic and antipyretic used in the
treatment of rheumatoid arthritis or osteo-arthritis, anky-
losing spondylitis, being well tolerated by the organism and
with mild side effects that does not require treatment
interruption [14] (Fig. 1).
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1066
Scheme 1 The synthesis
mechanism of PLA-co-Asp
copolymer
Fig. 1 [2-(2,6-dichlorophenyl)-amino] benzene acetic acid monoso-
dium salt
PLA-co-Asp/diclofenac sodium systems were prepared
using two different PLA-co-Asp copolymers with PLA/
Asp molar ratios 2.33/1 (DDS1) and 1/2.33 (DDS2). The
systems were obtained by precipitation and solvent evap-
oration method, as follows. DDS1 system: 0.4 g copolymer
(PLA/Asp = 2.33/1) were dissolved in 4 mL acetone, at
30 °C, by stirring and 0.16 g diclofenac sodium in 7 mL
phosphate buffer solution, pH = 7.4. Drug precipitation in
the copolymer solution was achieved by dropping dic-
lofenac solution in the copolymer solution under stirring
with a magnetic stirrer (450 rot min-1), yellow–brown
microparticles were obtained. The copolymer/drug system
was maintained under stirring for 2 h, then it was left 24 h
at room temperature to allow physical complexation; sub-
sequently the solvent was evaporated by vacuum drying at
60 °C. Diclofenac sodium content in DDS1 was 28.5 wt%.
DDS2 system: 0.4 g copolymer (PLA/Asp = 1/2.33) were
dissolved in 5 mL chloroform, by stirring at room tem-
perature, and 0.254 g diclofenac sodium in 40 mL PVA
aqueous solution (1.0 wt% concentration). Precipitation
was done by dropping the polymer solution into the
drug solution under stirring with a magnetic stirrer
(450 rot min-1), yellow–brown microparticles were
obtained. Then, the same technique as for DDS1 system
was used. Diclofenac sodium content in DDS2 was 24 wt%.
In Vitro Drug Release Studies
Drug loaded systems were placed in a cellophane mem-
brane of 40 lm thickness and subsequently immersed in
20 mL phosphate buffer solution (pH = 7.4), at 37 °C.
The, samples were taken at regular time intervals. The
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J Polym Environ (2013) 21:1064–1071
buffer solution was each time replaced after the sample
removal and recording the UV absorbance at pre-estab-
lished time intervals. The amount of drug, released in the
buffer solution was measured spectrophotometrically. For
both systems, the UV absorbance of the solutions was
recorded at k = 275 nm, characteristic wavelength for
diclofenac. In similar conditions was done the dialysis of
the polymer matrix without drug and the UV absorbance of
the copolymer was substracted from the respective system
absorbances.
Characterization
Fourier transform infrared spectra (FT-IR) were recorded
on a spectrophotometer Vertex 70 model (Bruker, Ger-
many), with a resolution of 4 cm-1. The samples were
homogenized and pressed on KBr pellets.
1
H-NMR spectra of the copolymers were obtained on a
Bruker Avance DRX 400 NMR spectrophotometer model
(Germany), 400 MHz. The copolymers were dissolved in
acetone-d6; the sample concentration was about 5 wt%.
The analyses were carried out at 25 °C, all the chemical
shifts were reported in parts per million (ppm) using tet-
ramethylsilane (TMS) as internal reference.
UV–Vis spectra were recorded on a spectrophotometer
6305-UV/VIS, Jenway model (England).
Optical microscopy was conducted using an optical
microscope with light transmission Micros MCD-500
model (Austria), with video chamber incorporated.
The molecular weight of the synthesized copolymers
was determined by gel permeation chromatography tech-
nique (GPC), at ambient temperature. The system was
equipped with an adjustable flow capacity and constant rate
pump LC 1120 type and an evaporative mass detector PL-
EMD 950 type. It was also fitted out with columns PL-gel
5 lm MIXED-D and PL-gel 5 lm MIXED-C packed with
polystyrene/divinylbenzene copolymer. DMF was used as
a mobile phase at a flow rate of 0.7 mL min-1.
The particles size measurement was done on a Master-
sizer 2000 system, Malvern Instruments (England). The
J Polym Environ (2013) 21:1064–1071
system is constituted of an optical bank, which used laser
light He–Ne 632 nm/2mW, a dispersion unity of the sam-
ple Hydro 2000A type, equipped with stirrer, recirculation
pump, and ultrasonic device. The measurement domain
was between 0.020 and 2,000 lm.
Differential scanning calorimetry (DSC) analyses were
carried out by means of a power compensated calorimeter
Pyris Diamond (Perkin Elmer). The samples with 9–10 mg
weight were performed at least twice, in the temperature
range 20–150 °C, with 10 °C min-1 heating rate, under a
flow of nitrogen (20 mL min-1). Before the experiments the
device was calibrated for temperature and energy using pure
indium as standard. The Tg values were determined at half of
the heat capacity step, from the second heating DSC run.
Thermogravimetric analyses (TG-DTG) were performed
by means of a derivatograph Q-1500 D (MOM Budapest
Hungary), at the following conditions: the weight of the
sample 50 mg, the heating rate 10 °C min-1, the maximum
heating limit 700 °C. The samples were heated in an open
Al2O3 crucible and Al2O3 as.reference material was used.
Results and Discussion
FT-IR and 1H NMR Characterization
To investigate the chemical structure of PLA and PLA-co-
Asp copolymer, FT-IR spectra (Fig. 2), were recorded. In
the FT-IR spectrum of PLA, can be observed the presence
of absorption bands characteristic to hydroxyacids, the
positions of these bands are in agreement with the literature
data [15]. At 3,506 cm-1 is recorded the absorption band
(tOH) that is attributed to the OH groups. At
2,945–2,985 cm-1, and 2,882 cm-1 are recorded the
stretching vibrations characteristic to tCH3 and tCH ali-
phatic groups, respectively; the pronounced absorption
band at 1,755 cm-1 is ascribed to the stretching vibrations
tCO from COOR groups. Asymmetric and symmetric
bending deformation vibrations dasCH3 and dsCH3 are
recorded at 1,454 and 1,386 cm-1, respectively. The
deformation vibrations dCH are also noticed at
1,269 cm-1, stretching vibrations mCO from COOR groups
at 1,180 cm-1 and deformation vibrations (tC–OH) spe-
cific to secondary alcohols at 1,094–1,130 cm-1. In
copolymer spectrum the most important is the absorption
band at 1,731 cm-1, characteristic to the ester groups
resulted in the polycondensation reaction. At 1,420 cm-1
exists a characteristic band mC=O from COOH group, and
at 1,526 cm-1 an absorption band characteristic to second
amide band (dNH and mCN) from –CONH– group. How-
ever, the absorption shoulder at 1,660 cm-1 from the first
amide band of –CONH– group was not obvious, and this
phenomen was similar to the reported literature [16].
1067
Fig. 2 FT-IR spectra of PLA and PLA-co-Asp copolymer
Besides, some specific absorption bands are recorded,
demonstrating that the polycondensation reaction took
place, e.g. the appearance of a pronounced absorption band
at 1,212 cm-1 that can be assigned to mC–N and dNH,
characteristic to CONH third amide group of secondary
amides (CONHR). These data in the FT-IR spectrum of the
copolymer are a strong indication that Asp chain segments
have been introduced in its structure.
Also the chemical structure of the copolymer, was
investigated by 1H-NMR spectrum (Fig. 3), (acetone-d6 as
solvent and TMS as internal reference). Based on the
reports of peak assignments for proton species in PLA and
derivatives in [7, 16], we assigned the proton signals in the
1
H-NMR spectrum of the PLA-co-Asp synthesized, as
follows. The methyl protons of PLA segments, were
recorded at 1.33 ppm (s, Hi from CH3 in the end of PLA
segment), 1.43 ppm (m, Hb from CH3 in PLA segment),
1.59 ppm (d, Hb from CH3 in PLA segment), 2.82/
3.33 ppm (m, Hd from CH2 in Asp and succinimide seg-
ments), 4.34–4.36 ppm (d, Hh from CH in the end of PLA
segment), 5.19–5.24 ppm (m, Ha from CH in PLA, Asp
and succinimide segments) the methine protons of suc-
cinimide overlaps with PLA methine resonance. At
5.40–5.50 ppm exist (m, Hg from OH in the end of PLA
segments), at 7.21 ppm (m, He from alchil–NHCO group)
and at 7.96–8.0 ppm (m, Hc from NH in amide bonds).
Acetone-d6 signal appeared at 2.10 ppm. The data obtained
from FT-IR and 1H-NMR spectra indicated that PLA-co-
Asp copolymer was obtained.
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Fig. 3 1H-NMR spectrum of

PLA-co-Asp copolymer

Molecular Weight PLA/Asp 2.33/1 (Tg = -19.02 °C) and 1/1 (Tg = -9.96 °C),
suggesting the presence of more amorphous regions and
The average molecular weights of the synthesized atactic structures.
copolymers, estimated from GPC data are given in Table 1.
From the data recorded can be noticed that the average
molecular weights of PLA-co-Asp copolymers are more
raised when PLA or L-aspartic acid exist in excess in the
polycondensation reaction. In this case, beside polycon-
densation, catalysed by manganese acetate, polyamidation
reactions have taken place simultaneously between COOH
groups present in PLA and NH2 groups from L-aspartic
acid (in the presence of H3PO4 and higher temperature in
the second stage). In the case of PLA-co-Asp copolymer
with molar ratio 1/1 the probability that both reactions take
place simultaneously is more reduced, consequently Mn is
lower. The polydispersity is low, all values being close to
unit.

Thermal Characterization
Fig. 4 DSC curves: 1 PLA-co-Asp (2.33/1); 2 PLA-co-Asp (1/1);
In Figs. 4 and 5 the thermal characteristics of the copoly- 3 PLA-co-Asp (1/2.33); PLA
mers, determined by differential scanning calorimetry are
presented. The glass transition temperatures (Tg) of the
copolymers have lower values comparative to PLA
(6.74 °C). In the case of the copolymers with molar ratio

Table 1 Average molecular weights of PLA and copolymers

Copolymer Mn Mw Mz Mw/Mn

PLA 2,026 2,987 4,326 1.474

PLA-co-Asp (2.33/1) 9,052 9,941 10,952 1.098
PLA-co-Asp (1/1) 5,815 6,350 6,970 1.092
PLA-co-Asp (1/2.33) 10,362 11,541 12,999 1.114 Fig. 5 Glass transition temperature: 1 PLA-co-Asp (2.33/1); 2 PLA-
co-Asp (1/1); 3 PLA-co-Asp (1/2.33); PLA

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In the case of PLA-co-Asp copolymer (1/2.33), Tg has
recorded an increased value 11.84 °C, comparatively to
PLA, possible due to grafted chains present in the
copolymer when L-aspartic acid was used in excess. The
specific thermal capacities (DCp) of the copolymers with
molar ratio 1/2.33 and 1/1 are 0.492, and 0.699 J/g °C
respectively, values close to the specific thermal capacity
of PLA (DCp = 0.665 J/g °C); PLA-co-Asp copolymer
(2.33/1) has a high value of specific thermal capacity value
(DCp = 1.508 J/g °C), suggesting that this copolymer
contained the most amorphous fractions, fact demonstrated
also by the low Tg value.
The thermal behavior of the copolymers, analyzed by
thermogravimetry (TG) and the obtained data are presented
in Fig. 6 and Table 2. The thermal stability of the
copolymer with molar ratio PLA/Asp (1/2.33) is higher
with weight losses of 50 wt% at 308 °C, while in the
copolymer with molar ratio 2.33/1 the same losses take
place at 285 °C. Also, the weight losses (W) on Ti–Tf
temperature interval indicated the same behavior. The
presence of aspartic acid in the copolymers structure
increased the thermal stability of the copolymers, com-
paratively to PLA (with number average molecular weight
Mn = 2,026). The activation energy (Ea) and the reaction
order (n) were determined by Coats-Redfern method [17],
on Ti–Tf temperature interval. From the data presented in
the Table 2 can be noticed that the values of these
parameters record a slight increase with aspartic acid ratio
increase.
Particle Size Distribution
The analysis of the dimensional distribution of copolymer
particles PLA-co-Asp and of the copolymer/drug systems
are presented in Fig. 7 and Table 3. Generally, it can be
noticed that the particles’ diameter of the copolymer/drug
systems is smaller than of the copolymer. In the case of
DDS1 system, 90 % of the total volume of the particles
have d \ 39.4 lm, and in the case of DDS2 system
d \ 115.2 lm, while the PLA-co-Asp copolymer has par-
ticles with d \ 354.8 lm. In the case of the copolymer/
drug systems the size of the particles (specific surface area)
influenced the delivery degree of the drug. The width of the
dimensional distribution (span) has values of 7.583 in the
case of the copolymer, respectively 2.11 and 3.67 in the
case of the copolymer/drug systems. When the span value
is smaller, the distribution is narrower.
Diclofenac Sodium Release
The concentration of diclofenac sodium released was
determined from the UV spectra absorptions, recorded by
dialysis of the copolymer/drug systems and from the cali-
brating curve of diclofenac sodium and adequate linear
equation. In Fig. 8 is presented the diclofenac sodium
release, in phosphate buffer solution (pH = 7.4), at 37 °C.
It can be noticed that diclofenac sodium released in the first

Fig. 7 Particle size distribution: 1 PLA-co-Asp; 2 DDS1; 3 DDS2

Fig. 6 TG curves of PLA and PLA-co-Asp copolymers

Table 2 Thermal parameters determined by thermogravimetry

Sample Ti (°C) Tm (°C) Tf (°C) WT–Tf (wt%) T10 (°C) T50 (°C) Ea (kJ/mol) n

PLA-co-Asp (2.33/1) 110 280 410 91.8 205 285 44 0.9

PLA-co-Asp (1/1) 120 320 410 90.2 220 305 49 0.9
PLA-co-Asp (1/2.33) 160 320 420 74.8 170 308 64 1.3
PLA 130 325 420 94.8 225 295 66 1.1
Ti, Tf the initial and ultimate temperature of the domain on which Ea and n were calculated, Tm the temperature corresponding to weight losses
with maximum rate, W mass losses, T10, T50 temperature corresponding to 10 and 50 wt% weight loss, Ea, n the activation energy and reaction
order

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Table 3 Characteristics of the copolymer/drug particles

Sample d(0.1) lm d(0.5) lm d(0.9) lm D[3.2] lm D[4.3] lm Uniformity Span

PLA-co-Asp 9.596 45.52 354.80 15.253 128.054 2.32 7.583

DDS1 5.281 16.14 39.434 9.792 25.765 1.02 2.119
DDS2 4.239 30.23 115.213 8.742 54.713 1.37 3.671
d(0.1); d(0.5); d(0.9)-10, 50, and 90 % of the sample volume are particles with a smaller diameter than the specified values in the table
[D3.2] medium diameter for the equivalent sphere of the same surface with that of the particle, called also media Sauter, D [4.3] medium
diameter for the volume of the equivalent sphere with the same volume with that of the particle, Uniformity is a measure of the absolute deviation
from the median value, Span represents the width of the distribution and the value is calculated with the relation: [d(0.9) - d(0.1)]/d(0.5)]

homogeneous aspect, in which dispersed microparticles

could be observed (Fig. 9a). In the case of the copolymer/
drug systems (Fig. 9b, c) the surface presented a hetero-
geneous aspect, due to the presence of two phases:
copolymer-drug. After precipitation, the drug was covered
by the polymer matrix as a shell through which diffused the
drug during dialysis.

Conclusions

In pharmaceutics are required macromolecular carriers

Fig. 8 Diclofenac sodium release from DDS1 and DDS2 systems
dialysis hours took place with the same speed in the case of
both systems. Nevertheless, at the end of the dialysis time
(356 h), diclofenac sodium released from DDS1 system
was 62.47 wt% from the whole quantity of drug present in
the system, and from DDS2 only 36.09 wt%. The more
reduced release from DDS2 system was possibly due to the
fact that diclofenac sodium was initially dissolved in the
PVA 1 wt% solution, which could act as a semipermeable
membrane and was also influenced by the copolymer used
in DDS2 (the molar ratio PLA/Asp = 1/2.33). The pres-
ence of the PVA macromolecular chains and PLA-co-Asp
copolymer that contains free COOH groups (due to
increased Asp content) determines probably PVA cross-
linking and hydrogen linkages and decreases the aqueous
dissolving capacity.
The morphology of the films surface was studied by
light transmission optical microscopy (Fig. 9). The
obtained PLA-co-Asp copolymer films presented a
with a certain hydrophobic/hydrophilic balance (to
improve the affinity with various kinds of drugs) and low
molecular weights. For this reason, PLA-co-Asp copoly-
mers were synthesized with molecular weight of 5,000/
10,000 Da. and low polydispersity index (between 1.09
and 1.11). The synthesized copolymers consist of lactic
acid and aspartic acid units, the latter being probably
mainly in the cyclic succinimide form. Subsequently, the
copolymers with molar ratios PLA/aspartic acid 2.33/1
(DDS1) and 1/2.33 (DDS2) were included in pharmaceu-
tical drug delivery systems, by complexation with dic-
lofenac sodium. Generally, the glass transition
temperatures of the copolymers (with molar ratios PLA/
Asp 2.33/1 and 1/1, respectively) had much lower values
comparatively to PLA suggesting the presence of many
amorphous regions. The presence of aspartic acid in the
copolymers structure determined a better thermal stability
than of PLA, the activation energy and the reaction order
recorded a slight increase with aspartic acid ratio increase.
The diclofenac sodium released from DDS1 and DDS2
systems showed that it was dependent of the initial molar

Fig. 9 Light transmission

optical microscopy: a PLA-co-
Asp (magnitude 10*), b PLA-
co-Asp/diclofenac sodium
(40*), c PLA-co-Asp/PVA/
diclofenac sodium (20*)

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ratios of the matrix components (hydrophilic/hydrophobic
ratio) (PLA/Asp 1/2.33 and 2.33/1) and of the particle size.
Diclofenac sodium was released 68.76 % from DDS1 and
only 36.09 % from DDS2, after 356 h dialysis time.
Taking into account the recorded results, the synthesized
copolymers would be possible biodegradable carriers in
controlled drug delivery systems. Also their low molecular
weights and glass transition temperatures would suggest
the same opportunity.
Acknowledgments The authors are grateful for the financial sup-
port from the Romanian National Authority for Scientific Research
CNCS–UEFISCDI, project: Interdisciplinary research on multifunc-
tional hybrid particles for bio-requirements ‘‘INTERBIORES’’ PN–
II–PT–PCCA–2011–3.2–0428, Grant no. 211/2012, and project Bi-
nanomed: Antimicrobial bionanocomposites for medical applications,
Grant PCCA/II, no. 164/2012, CNCCS–UEFISCDI.
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