Synthesis of Poly(D,L-lactic acid-co-Glucose) via Direct Polycondensation and its Characterization

Shihe Luo1,a, Zhaoyang Wang1,b, Dongna Huang1,c, Chaoxu Mao1,d, Jinfeng Xiong1,e

1School of Chemistry and Environment, South China Normal University, Guangzhou, Guangdong, 510006, China

apinky_r@163.com, bwangwangzhaoyang@tom.com (corresponding author), cdongnahuang@163.com, dmaochaoxu123@126.com, e669043583@qq.com

Keywords: Biodegradable material, Star-shaped Poly(lactic acid) (SPLA), D,L-lactic acid (D,L-LA), Direct Melt Polycondensation, Synthesis, Characterization.

Abstract. Directly using cheap D,L-lactic acid (D,L-LA) and glucose (Glu) as starting materials,

biodegradable material poly(D,L-lactic acid-co-Glucose) [P(D,L-LA-co-Glu)] was synthesized via

melt polycondensation. When n(Glu) : n(D,L-LA) = 1:200, the appropriate synthetic condition is that:

after 120 °C prepolymerization for 5 h, 160 °C melt polymerization catalyzed by w(SnCl2) = 0.5% for

5 h. P(D,L-LA-co-Glu) with different molar feed ratios were synthesized and characterized with [η],

FTIR, 1H NMR, GPC and XRD. The Tg of all copolymer P(D,L-LA-co-Glu) was lower than that of

homopolymer polylactic acid directly synthesized via melt polycondensation. The copolymers with

Mw from 2,100 Da to 5,100 Da could meet the demand of drug delivery carrier material.

Introduction

As a kind of important biodegradable aliphatic polyester, polylactic acid (PLA) is wholly

environment-friendly. Its excellent biocompatibility and biological resorbability afford it extensive

applications in bioplastic, biomedical polymer and other fields [1, 2]. Even so, recently more and

more attentions have been attracted to star-shaped PLA (SPLA) to improve the properties of PLA,

such as the unsatisfactory degradation rate [3-6]. At the same time, more interests have been also

focused on the modification of PLA by functional molecules to improve the poorer hydrophilicity and

the worse cell affinity [4, 6].

In this paper, on the basis of our preliminary researches on the direct melt copolycondensation of

lactic acid (LA) with other monomers [3-8], using glucose (Glu) as a functional molecule and a core,

and using cheap D,L-lactic acid (D,L-LA) as starting material, a novel SPLA biodegradable material,

poly(D,L-lactic acid-co-Glucose) [P(D,L-LA-co-Glu)] was synthesized via the simple and practical

melt polymerization (Scheme 1), and systematically characterized with the intrinsic viscosity [η],

FTIR, 1H-NMR, GPC, DSC and XRD.

Cat.+ 5n HO C

OHC

CH3

OHC

OHC

CH3

O H

R

n

O

HO

OH

OH

CH2OH

HO O

RO

OR

O

CH2OR

RO

a

b

c

d

e

f g

h

Scheme 1 Synthetic route of SPLA directly from D,L-LA and Glu

Experimental

Apparatuses and Materials. D,L-LA was purchased from Guangzhou Chemical Reagent Factory

(Guangdong, China), and glucose was purchased from Damao Chemical Reagent Factory (Tianjin,

China). Other analytic reagents, including stannous oxide, chloroform, methanol, were commercially

available.

Applied Mechanics and Materials Vols. 80-81 (2011) pp 370-374Online available since 2011/Jul/27 at www.scientific.net© (2011) Trans Tech Publications, Switzerlanddoi:10.4028/www.scientific.net/AMM.80-81.370

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1H-NMR spectra were recorded with a Varian NMR system 400 MHz (USA) with CDCl3 as the

solvent and TMS as internal standard. IR spectra were obtained from an FTIR spectrometer (Bruker

Vector 33, Ettlingen, Germany) by the CH2Cl2 liquid film method.

The [η] was determined with Ubbelohde viscometer (Cannon-Ubbelohde, State College, PA)

using CHCl3 as solvent at 25 °C. The relative molecular weight and molecular weight distribution of

the polymer were determined by gel permeation chromatography (Waters 1515 pump, Torrance, CA)

with tetrahydrofuran as solvent at 35 °C and a flow velocity 1 mL·min-1

.

DSC was performed with Perkin-Elmer DSC7 thermal analyzer (Perkin-Elmer, Cetus Instruments,

Norwalk, CT) at a heating rate of 10 °C•min-1

under a nitrogen atmosphere (flow velocity 20

mL·min-1

). The crystallinity of copolymer was investigated by XRD on a PANalytical X’pert PRO

X-ray diffractometer (PANalytical Co., Holland) using CuKα radiation with a wavelength of 1.5418

×10-10

m, and scanning range 2θ = 5-50° at a scanning speed of 0.03 deg·min-1

.

Melt Copolymerization. After prepolymerization, catalyst stannous chloride was added in according

to 5 wt % (weight percent) of dehydrated reactants. The melt copolymerization was carried out at 160

°C and an absolute pressure of 70 Pa for 5 h. When the reaction finished, the purification via the

dissolution in CHCl3 and the subsequent precipitation by CH3OH/H2O produced a yellowish or white

powder after drying in vacuo.

Results and Discussion

Optimal synthetic conditions for P(D,L-LA-co-Glu). The optimal synthetic conditions for the

copolymer, including the influences of catalyst kinds and dosage, melt copolycondensation time and

temperature on the synthesis of P(D,L-LA-co-Glu) were first investigated.

Catalyst played an important role in the direct melt polycondensation of D,L-LA, and usually tin

catalysts gave the best effect for their good dispersibility in the reaction system. The influences of

different catalysts on reaction are shown as Table 1 (runs 1-5). Among the catalysts, including SnO,

SnCl2, ZnCl2, TSA and ZnO, the [η] was biggest when using SnCl2 as the catalyst (run 1). Thus,

SnCl2 was selected as the catalyst for the following experiments because it was most likely to

generate the bigger molecular weight.

Table 1 The influences of catalyst on the reaction

Run Catalyst Catalyst dosage / wt% Appearance of product [η] /(dL·g-1

) Yield / %

1 SnCl2 0.3 Yellowish 0.8365 22.99

2 SnO 0.3 Brown yellow 0.5819 27.91

3 ZnO 0.3 Brown yellow 0.7377 26.27

4 ZnCl2 0.3 Brown yellow 0.7514 16.42

5 TSA 0.3 Yellowish 0.8222 17.79

6 SnCl2 0.1 Brown yellow 0.5957 13.41

7 SnCl2 0.5 Yellowish 1.0621 22.71

8 SnCl2 0.7 Yellowish 0.8083 30.38

9 SnCl2 0.9 Yellowish 0.7517 23.81

The influences of different SnCl2 catalyst quantities are also shown as Table 1 (runs 1, 6-9).

Usually, the metallic catalysts, including SnCl2, have double-side effects. They could accelerate the

polymerization, but also make the thermal decomposition of the product catalyzed. Therefore, neither

too much nor too little is suitable for the catalyst concentration. And for this reaction, the best

quantity of SnCl2 was 0.5 wt % (run 7).

The influences of different melt copolymerization temperatures on reaction are shown as Table 2

(runs 1-5). When the temperature was 140 °C, the lower temperature was disadvantageous for

polycondensation to remove the produced water from the reaction system, and the reaction gave a

yellowish product with the smallest [η] (0.6244 dL·g-1

, run 1). Increasing the temperature to 160 °C

Applied Mechanics and Materials Vols. 80-81 371

yielded the biggest [η] (1.0905 dL·g-1

, run 4). But at the higher temperature, the [η] decreased, even

the color of the product began to become yellow due to the side-reactions, such as the thermal

decomposition and oxidation (run 5). Thus, the suitable temperature should be 160 °C.

Table 2 The influences of polymerization on reaction

Run Temperature / °C Time / h Appearance of product [η] /(dL·g-1

) Yield / %

1 120 5 Yellowish 0.6244 19.43

2 140 5 Brown 1.0621 22.71

3 150 5 Yellowish 1.0702 17.78

4 160 5 Yellowish 1.0905 30.92

5 170 5 Yellow 0.8364 13.95

6 160 3 Yellowish 0.4826 49.38

7 160 7 Yellowish 0.8980 48.14

8 160 9 Yellowish 0.8788 35.76

9 160 11 Yellowish 0.7092 38.72

The influences of melt copolymerization time on reaction are shown as Table 3 (runs 4, 6-9).

Obviously, the suitable time should be 5 h. The reason is similar to the above discussion, but mainly

due to the influence of the balance between polycondensation and thermal decomposition. Therefore,

When n(Glu) : n(D,L-LA) = 1 : 200, the appropriate synthetic condition is that: after 120 °C

prepolymerization for 5 h, 160 °C melt polymerization catalyzed by w(SnCl2) = 0.5% for 5 h. Under

these conditions, the biggest [η] was 1.0905 dL·g-1

, and GPC determination showed that the

corresponding Mw was 2400 Da.

Structure characterization of P(D,L-LA-co-Glu). Using P(D,L-LA-co-Glu) with a molar feed ratio

n(Glu):n(D,L-LA) of 1:200 as an example, the structural characterization showed in their FTIR

spectra with the strong absorption of ester carbonyl at 1757.15 cm-1

. The absorptions at 952.84,

869.90, 756.10, 686.66 cm-1

were the characteristic absorptions of glucose, and the OH absorption at

3522.02 cm-1

in copolymer also became stronger and broader than that in homopolymer PLA, e.g.

poly(D,L-lactic acid) (PDLLA) synthesized via direct melt polycondensation [9]. 1H-NMR data of P(D,L-LA-co-Glu) with a molar feed ratio n(Glu):n(D,L-LA) of 1:200, δ, ppm

(CDCl3 as solvent and TMS as internal standard): 1.486 (Hb, CH3 in PLA chain), 4.345~4.395 (Hc,

-CHCH2O- in Glu segment), 4.27 (Hi, terminal OH in terminal PLA segment), 5.158~5.176 (Ha, Hd~

Hh, CH in PLA chain and Glu segment). The structure of the copolymer P(D,L-LA-co-Glu) was

basically demonstrated by 1H-NMR as anticipated. Therefore, the examination of FTIR and

1H-NMR

indicated that the obtained products were copolymers, and core Glu was existed in the copolymer.

Relative Molecular Weight Distribution. When the molar feed ratio was different, the GPC results

are shown in Table 3. All GPC flow curves had only a single symmetrical peak, and all polydispersity

index (PDI) value (Mw/Mn) were less than 2, which indicated that the melt copolycondensation of

D,L-LA and Glu indeed only gave the copolymer.

It also could be seen that [η] and Mw didn’t increased with the increase of n(D,L-LA) : n(Glu). This

may be related to the special phenomenon and the reaction mechanism during the direct melt

copolycondensation of LA with the monomers containing multifunctional groups [4, 6, 7].

Usually, when the PLA biodegradable polymers were used as drug delivery material, their

molecular weights were no more than 30000 Da [8-10]. As reported in the literatures, the PLAs

material with molecular weight of 1800 Da could be applied in drug delivery, even the PLA polymers

with molecular weight of only 900 Da could be used as drug delivery material [8, 11, 12]. All

molecular weights of SPLA synthesized here via the direct melt copolycondensation are

overwhelmingly higher than 900 Da. Therefore, the Mw could meet the requirement for drug delivery

application at the least.

372 Information Engineering for Mechanics and Materials

Table 3 The GPC results of the copolymers P(D,L-LA-co-Glu)s

n(Glu) :

n(D,L-LA)

Appearance

of product Mn Mw Mw / Mn

[η] /

(dL·g-1

)

Yield

/ %

Tg

/°C

Tm

/°C

1 : 50 Brown yellow 2000 2700 1.38 0.4826 43.86 22.36 ND

a

1 : 100 Yellowish 2600 3900 1.52 0.4684 42.56 30.03 137.5

1 : 150 White 1900 2600 1.36 0.5109 48.16 20.26 ND

a

1 : 200 Yellowish 1800 2400 1.30 1.0905 30.92 20.88 132.66

1 : 500 Yellowish 3200 5100 1.60 0.8927 39.28 34.80 ND

a

1 : 750 Yellowish 3000 4500 1.52 0.7512 38.45 32.97 ND

a

1 : 1000 Yellowish 1700 2100 1.28 0.7374 45.19 19.49 ND

a

1 : 1400 Yellowish 1800 2400 1.33 0.3976 48.34 21.17 143.78

a. Not detected.

Thermal Properties of SPLA. The data of DSC test on series samples are also shown in Table 3.

The value of all Tg was lower than that of the linear PLA (e.g. PDLLA synthesized via direct melt

polycondensation, Tg = 54.57 °C [9]). It also could be seen that, the observed Tm was higher than that

of PDLLA (Tm = 120.02 °C [9]). The reason was that the introduction of Glu as the core into SPLA,

and the introduction of Glu altered the regularity of PLA. These phenomena and conclusions were

consistent with the reported in the literatures [3].

Fig. 1 XRD spectrum of P(D,L-LA-co-Glu) with n(Glu):n(D,L-LA) of 1:200

Crystallinity of SPLA. The crystallinity of polymers has an important effect on their physical and

biological properties, especially their degradability which is crucial for biomaterials. The

introduction of Glu as the core into SPLA also made the crystallization behavior changed. In most

cases, the copolymer was amorphous. Even some peaks were found (Figure 1), though the

diffraction peak position of SPLA were basically consistent with that of the linear PDLLA, the

crystallinity was obviously lower than that of PDLLA (Table 4).

Table 4 The XRD result of the copolymer P(D,L-LA-co-Glu) with n(Glu):n(D,L-LA) of 1:200

n(Glu) : n(D,L-LA) 2θ

Crystallinity / % Crystallite Dimension / 10

-10m

Face / 110 Face / 020 L110 L020

1 : 200 16.5 19.1 4.72 279 125

PDLLA [9] 16.7 19.1 20.8 154.4 83.9

Fortunately, lower or no crystallinity is more beneficial for PLA biodegradable materials to be

applied in the biomedical fields, especially drug delivery carrier materials, because there will be no

residual microcrystalline after degradation in vivo.

Applied Mechanics and Materials Vols. 80-81 373

Summary

A novel biodegradable material P(D,L-LA-co-Glu) was synthesized via melt polycondensation.

The appropriate synthetic conditions were discussed. The systematical characterization showed that,

the obtained copolymer could meet the demand of drug delivery carrier material.

Acknowledgements

We are grateful to Guangdong Provincial Natural Science Foundation of China (No. 5300082) and

National Natural Science Foundation of China (No. 20772035) for the financial support of this work.

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Information Engineering for Mechanics and Materials 10.4028/www.scientific.net/AMM.80-81 Synthesis of Poly(D,L-Lactic Acid-Co-Glucose) via Direct Polycondensation and its Characterization 10.4028/www.scientific.net/AMM.80-81.370

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http://dx.doi.org/10.1163/156856297X00272