Poly(L-lactide)-Poly(ethylene glycol) Multiblock Copolymers: Synthesis and Properties

Chinese Chemical Letters Vol. 13, No. 1, pp 33 - 36, 200233http://www.imm.ac.cn/journalcc.htmlPoly(L-lactide)-Poly(ethylene glycol) Multiblock Copolymers:Synthesis and PropertiesWei Jun LUO, Su Ming LI, Jian Zhong BEI, Shen Guo W ANG*Center fpr Molcular Science, Institute of Chemistry, Chinese Academy of Sciences,Beijing 100080Abstract: Poly (L-lactide)-poly(ethylene glycol) multiblock copolymers with predetermined blocklengths were synthesized by polycondensation of PLA diols and PEG diacids. These copolymerspresented special properties, such as better miscibility between the two components, lowcrystallinity and better hydrophilicity, which can be modulated by adjusting the block lengths ofthe two components.Keywords: Poly (L-lactide), poly(ethylene glycol), biodegradability, multiblock copolymer,miscibility, crystallinity, hydrophilicity.Recently， growing interest was given to a new class of biomaterials: the polyether-polyester block copolymer. Poly (ethylene glycol) (PEG) and poly (-lactide) (PLA) arethe most widely used polyether and biodegradable polyester components, owing to theiroutstanding properties. Copolymerization offers the possibility to combine thehydrophilicity of PEG and biodegradability of PLA and lower the crystallinity of thecopolymers to make a wide rang of polymeric materials for medical applications.Various PLA-PEG block copolymers synthesized by different ways have been reported,and they showed versatility in both mechanical as well as biodegradation properties 1-4.However almost all of these copolymers are triblock. It appears interesting to considerthe multiblock ones. Lee et al. have prepared such PLLA - PEG multiblock copolymers,and investigated the crystallization behavior of the copolymers'. However a muchwider investigation should be done on the molecular structure, characterization theproperty of the PLLA - PEG multibock copolymers. Compared to the triblock one withequal Mn, multiblock copolymer has more and shorter PEG and PLA segments, whichalternate in the polymer chain. Consequently, it is possible to get some specialproperties such as better miscibility between the two components and lower crstallinity.Thus the degradability of the copolymer is expected to be enhanced.The synthetic procedure of the PLA - PEG multiblock copolymer can be outlined asScheme 16-8. Along this way, a series of muliblock copolymers with different PEG andPLA segments were synthesized. The multiblock copolymers are presented as PLAx-PEGy, where x and y are the molar mass of the PLA and PEG macromonomersrespectively. Table 1 gives out some direct information about all the related polymers.中国煤化工MHCNMH G.34Wei Jun LUO et al.Scheme 1 Outline of synthetic procedureHO- (CH2CH2O)m-H+20 y=O- Py.CHC3 H0OCCH2CH12C0O -PEO -C0CH2CH2COOH (1)55°C( PBG)( H0OC- PEO-COOH )2nHOCH2CH2OHZn _ + H(OCHCO)n- 0CH,CH20-(COQHO)r-H(2)140°CCH(L-LA)( HO-PLA-OH )DCC; DMAPm HOOC-PEO- -CO0H + mHO-PLA-OH25C+0c -PEO -C00 -PLA-O+m .(3In all cases, the copolymers exhibited unimodel molar mass distribution in GPC graphs.In other words, the copolymers did not contained unreacted PEG diacids or PLA diols.The molar masses and [n] of copolymers are much higher than those of the startingmacromonomers.Table 1 Molar mass and [n] data of PLA- PEG multiblock copolymersCopolymerMw*/103Mn*/10Mw/Mn*PLLA/PEG'[η]PLA 1000 - PEG 60014.311.031.040.28PLA 2000 - PEG 60027.418.11.50.950.48PLA 3000 - PEG 60030.720.3.51.000.50PLA 1000 - PEG 20003.20.860.33PLA 2000 - PEG 200016.711.30.45PLA 3000 - PEG 20001.080.38"Determined by GPC measurement.”Molar ratio of the two component segments in the copolymers, calculated from 'H NMR spectra.H NMR spectrum of the multiblock copolymers was done. It could be seen thatthe spectrum bands of methylene protons end units of succinic anhydride half estermoved appreciable distance down to low field after copolymerization. And the bandcorresponding to-CH- in PLA end groups moved from 4.33 ppm to 5.13 ppm. Thesemotions constitute evidences that copolymerization happened between the twomacromonomers and there were few end function groups remain unreacted. Thethermal properties of the compolymers and their macromonomers were investigated byDSC. Each of copolymers showed only one meditated Tg rather than two separated.That means the two components got some miscibility in the multiblock copolymer, atleast in the amorphous domain, rather than incompatible in the mixture of theirhomopolymers' as well as in PEG-PLA- PEG triblock copolymers 3In all cases, PEG and PLA segments showed decreased crystallinity aftercopolymerization due to the hindrance between each other. The longer the segmentlength of one component is, the higher its crystallinity and the lower the crystallinity forthe other component, as shown in Table 2. The X-ray diffraction analysis result of themarcromonomers and multiblock copolymers agree well中国煤化工YHCNMH G.Poly(L-Lactide)-Poly(Ethylene Glycol) Multiblock Copolymers35measurement.Table 2 Crystallinity of PEG and PLA segments in the multiblock copolymers#Crytallinity: PEG segmentPLA segmentSegmentPLA 1000PLA 2000PLA 3000PEG 600-'\+PEG 2000+\+\+-\++ means crystalline, - means amorphousFigure1 shows the contact angle vs. time curves of the copolymers and PLAmacromonomer. PLA macromonomers had almost the same initial contact angle (72-73° ). The initial contact angles of the copolymers was in the range of 44 to 67° , whichwere lower than those of PLA macromonomer. The contact angle to time curves ofPLA 2000 - PEG 600 and PLA 3000 - PEG 6000 showed similar trends as PLA, i.e.almost linear decrease with time. In contrast, the other copolymer, namely PLA 1000 -PEG 600, PLA 1000- PEG 2000, PLA 2000 - PEG 2000 and PLA 3000 - PEG 2000,presented a very rapid decrease of contact angle. That means that the hydrophilicity ofthese copolymers was greatly improved. Even PLA 2000 - PEG 600 and PLA 3000 -PEG 600 showed higher hydrophilicity than corresponding PLA macromonomer.In conclusion, multiblock PLA - PEG copolymer was successfully synthesized bypolycondensation of PLA diol and PEG diacid. This copolymer showed an improvedmiscibility between the two components. The crystallinity of the copolymers wagreatly decreased in comparison with PLA and PEG homopolymers, and it could bemodulated by adjusting the block lengths of both components. Contact anglemeasurement confirmed the strong improvement in hydrophilicity as referred to PLAhomopolymer. These properties should be interesting for biomedical uses, in particularas drug carrier for controlled releasing as well as cell scaffold material in tissueengineering.Figure 1 Contact angle vs. time curves of PLA3000 and two compolymers70PLA3000656015PLA3000-PEG600”20PLA1000-PEG60015100200 400 600 800 1000 1200 1400Time (second)中国煤化工MHCNMH G.36Wei Jun LUO et al.AcknowledgmentThe authors are indebted to the National Basic Science Research and Development Grants (973)(No. 1999054306).References1. D. Cohn, HYounes,J. Biom. Mater. Res, 1988, 22, 993.X. M. Deng, C. D.Xiong, L. M. Cheng, R. P. Xu, J. Polym. Sci, Part C, Polym. Lelt, 1990,28, 411K.J .Zhu, x. Z .Lin, s. L. Yang, J. Appl. Polym. Sci, 1990, 39, 1.P. Cerrai, M. Tricoli, L. Lelli, G. D Guerra, R. Sbarbati Del Guerra, M. G Casone., P. Giusti,J.Mater. Sci. ,Mat. Med, 1994,5, 308.6. S. Lee, I. Chin, J. Jung, Eur. Polym. J, 1999, 35, 2147.P. Ferruti, M. C. Tanzi, L. Koleske, R. Cecchi, Macromol. Chem, 1981, 182, 2183.R. K. 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