Journal of Metals, Materials and Minerals, Vol.20 No.3 pp.

189-192, 2010

Functionalization of Poly(Lactic Acid) with Maleic Anhydride for Biomedical Application

Daorat MUENPRASAT1, Supakij SUTTIREUNGWONG1, 2* and Chanchai TONGPIN1, 2
1

Department of Materials Science and Engineering, Faculty of Engineering and Industrial Technology, Silpakorn University, Nakhon Pathom 73000 2 National Center of Excellence for Petroleum, Petrochemicals, and Advanced Materials, Chulalongkorn University, Bangkok 10330

Abstract
The aim of this work was to study the modification of Poly(lactic acid) (PLA) with maleic anhydride (MA) through free radical reaction in order to improve the hydrophilic property of PLA. The chemical bulk modification was carried out for all experiments. The concentrations of MA and benzoyl peroxide varied from 2 20wt% of PLA and 1-10wt% of MA, respectively. The effects of temperature and time on the reaction were studied. The samples were then characterized using FT-IR, 13C-NMR, DSC, acid-base titration method, contact angle testing and gel permeation chromatography (GPC). The results revealed that the modification of PLA with MA was successfully done. The MA grafted PLA (MA-PLA) exhibited more hydrophilicity when compared to the pure PLA. However, the molecular weights of MA-PLA decreased, probably due to the chain scission reaction. Key words: Poly(lactic acid), Maleic anhydride, Tissue engineering, Hydrophilicity

Introduction
Poly(lactic acid) (PLA) is a biodegradable and biocompatible polymer. The functionalization of poly(lactic acid) (PLA) is essential in terms of pharmaceutical and tissue engineering applications. Despite its good biocompatibility and biodegradability, PLA possesses some disadvantages such as hydrophobicity and thus poor cell attachment.(4-6) Many attempts have been made for grafting of maleic anhydride (MA) onto low molecular weight PLA such as number average molecular weight of 23,200 g/mol Plackett (3), 25,291 g/mol Pan, et al.(4), 50,500 g/mol Wu(7), 92,100 g/mol.(5) In this study, the functionalization of high molecular weight PLA with maleic anhydride (MA) was investigated via free radical reaction using benzoyl peroxide (BPO) as an initiator. The effects of BOP and MA concentrations, together with reaction time and temperature were studied.

were purchased from Scharlau. Low molecular weight of PLA ( Mw = 1.6013 x 105 g/mol) was obtained from reacting PLA with an excess amount of MA. Dichloromethane (analytical grade), chloroform (analytical grade) and diethyl ether (commercial grade) were purchased by RCI Labscan. Preparation of Maleic Anhydride Grafted Poly (Lactic Acid) Firstly, PLA 5 g, MA 0.1 g and BPO 0.001 g were all mixed in dichloromethane. After that the solution was kept in vacuum oven at room temperature for 24 hours. The solid mixture was then heated in the. The resulting product was collected and purified by dissolving in chloroform, and precipitating with diethyl ether. The resulting product, designated MA-PLA, was filtered and dried in vacuum at 40C for 10 hours. The experiments were repeated by varying MA from 2-20wt% of PLA and BPO from 1-10wt% of MA. The reaction time and temperature were varied from 10-20 hours and 90-120 C The common reaction scheme of MA with PLA to produce MA-PLA is shown in Scheme 1.(4)

Materials and Experimental Procedures

Materials PLA ( Mn = 2.9373 x 105 g/mol, Mw = 3.7217 x 105 g/mol) was purchased from NatureWorks. MA and BPO (synthesis grade)

*Corresponding author Tel: +66 3421 9363; Fax: +66 3421 9363; E-mail: supakij@su.ac.th

190 MUENPRASAT, D. et al.

BPO

PLA

PLA free radical

MA-PLA

Sheme 1. The reaction scheme for grafting of MA onto PLA by free radical reaction.(4) Characterization The chemical structures of PLA and MAPLA were investigated using VERTEX 70 fourier transform infrared spectroscopy (FT-IR) and The 13 C NMR spectra were obtained using Bruker Avance 300 NMR Spectrometer. The thermal properties were investigated using METTLER differential scanning calorimetry (DSC) operated under nitrogen in a heat-cool-heat cycle mode with heating rates of 10oC/min and a cooling rate of 5C/min. The grafting percentage was determined using a titration method.(2, 7) The acid number was calculated using equation (1) and grafting percentage calculated using equation (2).
Acid number(mgKOH/g) = VKOH (ml) x CKOH(N) x 56.1 Polymer (g) Grafting percentage (%) = Acid number x 98.1 x 100% 2 x 561 (1)

by other group.(6) In the physical mixture, these two peaks were not observed. The 13C NMR spectra of MA-PLA collected 2048 scans showed signals at chemical shifts of 20.49 and 66.70 ppm (Figure 2), which were assigned to the metgine and methylene carbons in the succinic anhydride rings formed when MA reacts with a tertiary radical site on the polyester backbone.(3) This result confirmed the existence of MA on PLA structure.
(a)

(b)

(c) (d)

Figure 1. FT-IR spectra of PLA(a), MA-PLA(b), the differential spectra of MA-PLA and PLA (c) and the physical mixture of PLA and MA(d).

(2)

66.70

Gel permeation chromatography (GPC), Hewlett Packard HP 1100, was used to determine the molecular weight of PLA and MA-PLA. Contact angle tester, Kruss/DSA 10 MK2, was used to investigate the hydrophilic properties of PLA and MA-PLA.
Figure 2. 13C-NMR Spectra of MA-PLA.

20.49

Results and Discussion

Chemical Structure For the determination of chemical structure of the resulting product, the modification started with the MA content of 2%wt of PLA and BPO concentration of 1% of MA. The comparison spectra as shown in Figure 1, revealed that the differential spectra of PLA and MA-PLA showed two new absorption peaks appeared at 1773 cm-1 and 1746 cm-1 (Figure 1(c)) similar to those found When compared the glass transition (Tg) peak of PLA and MA-PLA (Figure 3), Tg of MAPLA was less than that of PLA. This indicated that MA-PLA was more flexible than PLA. .(4)

191 Functionalization of Poly(Lactic Acid) with Maleic Anhydride for Biomedical Application between the grafting and the branching reaction.(1) Another possible explanation for this could be the dispersion of BPO content in the solid state of chemical bulk reaction which may lead to the poor distribution of free radical.

^ Exo

Grafting percentage(%)

0.6 0.4 0.2 0 1

0.65

Temperature ( C)

10

Figure 2. DSC (Exo up) of PLA and MA-PLA under nitrogen at a heating rate of 10C/min and a cooling rate of 5C/min.

BPO concentration (%wt of MA)

BPO concentration (% wt.)

Effect of MA Concentration The grafting percentages of MA-PLA with varying MA concentration were shown in Figure 4. The results indicated that when the amount of MA increased, grafting percentage also increased. The grafting percentage was not changed significantly when the MA concentration was more than 10wt%. One reason for that was, at a higher concentration of MA, the chain scission reaction of PLA may occur (5) and could compete with the grafting reaction.

Figure 5. Effect of initiator concentration on grafting percentage of MA- PLA with control : MA 10 wt% of PLA, reaction time 20 hours and temperature 110C.

Effect of Temperature and Reaction Time The temperature and the reaction time influenced the grafting reaction as shown in Figure 6 and 7. It was found that the suitable temperature and reaction time were 110C and 18 hours.

Grafting percentage(%)

0.6 0.4 0.2 0.0 90 100

0.65

Grafting percentage(%)

0.6 0.4 0.2 0.0 2 5

0.46

0.49

110
o

120

Temperature Temp (oC) ( C)

10

20

MA concentration (%wt of PLA) MA concentration (% wt.)

Figure 6. Effect of temperature on grafting percentage of MA- PLA with control : MA 10 wt% of PLA, BPO 2 wt% of MA and reaction time 20 hours. 0.65

Figure 4. Effect of MA concentration on grafting percentage of MA- PLA with control : BPO 1 wt% of MA, reaction time 20 hours and temperature 110C.

Grafting percentage(%)

0.6 0.4 0.2 0.0 10 12 14 16 18 20

Effect of Initiator Concentration The grafting percentages of MA-PLA with varying initiator concentration (fixed MA 10wt% of PLA) were shown in Figure 5. The highest grafting percentage was found to be 2 wt% of MA. When using higher amount of BPO, the grafting percentage decreased. This may be the competition

Time ( hr)
Figure 7. Effect of reaction time on grafting percentage of MA- PLA with control : MA 10 wt% of PLA, BPO 2 wt% of MA and temperature 110C.

192 MUENPRASAT, D. et al. The hydrophilicity results from contact angle testing of PLA and MA-PLA (Table 1) revealed that the contact angle of MA-PLA was higher than PLA, thus more hydrophilic when compared to PLA.
Table 1. Contact angle results of PLA and MA-PLA.
Sample PLA MA-PLA Contact Angle (o) 78.93, 79.43, 79.63 70.58, 70.98, 70.54

anhydrides in MA-PLA can be hydrolyzed into more polar carboxyl groups. This product will be further applied as tissue engineering scaffold in the future work.

Acknowledgements
This study was supported by the department of Materials Science and Engineering, Faculty of Engineering and Industrial Technology, Silpakorn University, Nakhon Pathom, and the National Center of Excellence for Petroleum, Petrochemicals and Advanced Materials, Chulalongkorn University, Bangkok.

Effect of PLA Molecular Weight In this study, the PLA with high and low molecular weights (160,130 g/mol) modified by MA were compared using the conditions obtained previously. Table 2 shows the grafting percentage and molecular weight of MA-PLA and PLA with two different molecular weights. From the table, it was found that both molecular weights of PLA decreased after the reaction. This could result from the chain scission reaction. The grafting percentage of low molecular weight was two times greater than that of the high molecular weight. The lower grafting percentage of high molecular weight could result from the entanglement of PLA molecules, which makes it difficult for the diffusion of reacting molecules to react with the PLA backbone.
Table 2. Effect of PLA molecular weight on grafting

References
1. Carlson, D., Nie, L., Narayan, R. & Dubois, P. (1999). Maleation of polylactide (PLA) by reactive extrusion. J. Appl. Polym. Sci. 72(4) : 477-485. 2. Wu, C.S. (2003). Physical properties and biodegradability of maleated-polycaprolactone/starch composite. Polym. Degrad. Stabil. 80(1) : 127-134. 3. Plackett, D. (2004). Maleated polylactide as an interfacial compatibilizer in biocomposites. J. Polym. Environ. 12(3) : 131-138. 4. Pan, J., Wang, Y.L., Qin, S.H., Zhang, B.B. & Luo, Y.F. (2005). Grafting reaction of poly (D,L)lactic acid with maleic anhydride and hexanediamine to introduce more reactive groups in its bulk. J. Biomed. Mater. Res. B 74B(1) : 476-480. 5. Luo, Y.F., Wang, Y.L., Niu, X.F., Fu, C.H. & Wang, S.J. (2007). Synthesis, characterization and biodegradation of butanediamine-grafted poly(DL-lactic acid). Eur. Polym. J. 43(9) : 3856-3864. 6. Cao, C., Zhu, F., Yu, X., Wang, Q., Wang, C., Li, B., Lv, R. & Li, M. (2008). Two-step modification of poly(D,L-lactic acid) by ethylenediamine-maleic anhydride. Biomed. Mater. 3(1) : -. 7. Wu, C.S. (2009). Renewable resource-based composites of recycled natural fibers and maleated polylactide bioplastic: Characterization and biodegradability. Polym. Degrad. Stabil. 94(7) : 1076-1084.

percentage of MA- PLA.

Molecular weight(g/mol) Material PLA MA-PLA Grafting percentage (wt%)

Mn
High molecular weight PLA Low molecular weight PLA 293,730

Mw
372,170

Mn
195,950

Mw
294,870 0.65

92,330

160,130

76,360

128,480

1.25

Conclusions
The fictionalization of PLA with MA was successfully done and the suitable condition of grafting reaction by this method with high molecular weight of PLA are MA 10 wt% of PLA, BPO 2 wt% of MA, reaction time 18 hours and temperature 110C. From the contact angle test, the hydrophilicity of PLA was improved. The molecular weights of MA-PLA tended to decrease probably due to chain scission by MA. Functionalized PLA with MA could improve the hydrophilicity and the cell affinity of PLA as the