Synthesis and Degradation of Poly (Diol Citric Itaconate) Polyester Elastomers
J. Margaret Marie*1,3, S. Santhi2,4, R. Puvanakrishnan3, and R. Nanthini4
1Department of Chemistry, Women’s Christian College, Chennai, India.
2Department of Chemistry, Bharathi Women’s College, Chennai, India.
3Department of Biotechnology, Central Leather Research Institute, Chennai, India.
4PG and Research Department of Chemistry, Pachaiyappa’s College, Chennai, India.
Corresponding author: margaretxavier@gmail.com
ABSTRACT:
Synthetic bioelastomers are a class of biomaterials that are extensively used for biomedical applications. A potential biomaterial is expected to be elastic and flexible, so that it could mimic the mechanical properties of natural tissues. In this paper, we report the studies on two elastomers: Poly(1,12-dodecanediol citrate-co-1,12-dodecanediol itaconate) [p(DDCI)] and Poly(1,4-cyclohexanedimethanol citrate-co-1,4-cyclohexanedimethanol itaconate) [p(CHCI)], containing multifunctional non-toxic monomers; citric acid (CA), 1,12-dodecanediol (DD), 1,4-cyclohexanedimethanol (CHDM) and itaconic acid (IA). Citric acid can undergo polycondensation in the absence of toxic catalyst. Also, its multifunctionality favours crosslinking of polymeric networks during thermal curing conditions. The polyester was characterized by Fourier transform infrared spectroscopy, 1H NMR spectroscopy and differential scanning calorimetry analysis. The Young’s modulus, UTS, % elongation and swelling experiments revealed that the mechanical and swelling characteristics of the polyesters revealed that it is can be fabricated as per the requirements of its biological applications. The solubility tests revealed that the pre-polymers were soluble in common organic solvents therefore facilitating processing ability for scaffold fabrication. The insolubility of post-polymerised polyester confirmed their elastomeric nature and was further evidenced by the glass transition temperature which was well below the body temperature. In vitro degradation studies were performed on the polyester samples. It was observed that the Young’s modulus and crosslink density were higher for [p(DDCI)] while the degradation rates of [p(CHCI)] was higher. This was attributed to the structural difference between the two diols and the degree of crosslinking between polymeric chains. As all the monomers used in the material have previously been utilized in other biomaterials the synthesized elastomer were expected to be excellent candidates as future biomaterials.
KEY WORDS: Citric acid; itaconic acid; 1,4-cyclohexanedimethanol; elastomer; polyester
Synthetic polyester elastomers are an important class of biomaterials that find wide spread applications in drug delivery, tissue engineering, gene therapy and packaging.1 Most of the biodegradable elastomers that have been developed require complex and costly synthesis procedures, which translate into higher manufacturing costs which hinder the commercial and clinical implementation of their use.2 Further, selection of monomers for biomaterial syntheses is crucial for determining and controlling the functionality and biocompatibility of the biomaterials to be produced.
Recently, there is an increased attention in using citric acid and itaconic acid as a robust multifunctional monomer for biomaterial syntheses.3 Several biodegradable polymers such as poly(glycerol sebacate), poly(octanediol citrate), poly(ethylene glycol-co-citric acid), poly(polyol sebacate and poly(glycerol citrate) have been synthesized and they are considered to be the new generation materials for potential biomedical applications. However, the synthesis of most of these polymers requires high temperature, vacuum and long post-polymerization time. Furthermore, these polymers cover only a modest range of mechanical and physicochemical properties.4
Herein, we report the synthesis and studies two polyesters: Poly(1,12-dodecanediol citrate-co-1,12-dodecanediol itaconate) [p(DDCI)] and poly(1,4-cyclohexanedimethanol citrate-co-1,4-cyclohexanedimethanol itaconate) [p(CHCI)]. To our knowledge no study has systematically investigated polyester elastomers combining citric acid and itaconic acid in combination with aliphatic diols as comonomer by catalyst-free melt polycondensation reactions. All the monomers used have been previously used in other biocompatible polymers and so cytotoxicity was expected to be low.
Synthesis of the polyesters
The pre-polymers were synthesized by catalyst-free melt-condensation technique. Equimolar amounts of diol (DD or CHDM) and acids [Diol:(CA+ IA) = 1:1] were placed in a three-necked round-bottom flask and the monomer mixture was first heated up to 160-165 °C followed by heating at 140-145 °C for 3 h under a constant stream of nitrogen. The pre-polymers thus obtained were dissolved in 1, 4-dioxane [20% w/w solution] and the resulting pre-polymer solution was used for film preparation without further purification.5 Films for mechanical and structural analysis were cast into Teflon petri dishes and placed in an air oven maintained at 80 °C for 24 h for post polymerization of the pre-polymers.
Fourier transform infrared (FTIR) spectra were obtained at room temperature (27 °C) using ABB MB 3000 FT-IR SPECTROMETER. Pre-polymer samples were prepared by a solution casting technique (5 % pre-polymer solution in dichloromethane) over a KBr crystal. The 1H NMR spectra for pre-polymers were recorded using a JOEL NMR spectrometer. The pre-polymers were purified by precipitation in water with continuous stirring followed by freeze-drying and they were then dissolved in CDCl3 in 5 mm outside diameter tubes. Solubility of all the prepolymers was determined in various solvents qualitatively. Differential scanning calorimetric (DSC) thermograms were recorded in the range of -70 °C to 150 °C using DSC Q200 V23.10 Build 79 at a heating rate of 1 °C min-1 under nitrogen. The mechanical properties of the polyesters were measured with Tinius Olsen h10K-S UTM testing machine the load cell is of 5 N. The dog bone-shaped polymer film strips were prepared according to ASTM D 628 (30 mm × 5 mm × 5mm; length × width × thickness) and pulled at a strain rate of 1 mm/min. Values were converted to stress-strain and plotted. Young’s modulus was calculated from the initial slope of the curve of the tensile stress versus strain.
Swelling Studies:
The percentage swelling of the polyester was measured in DMSO as follows: 10 mm diameter discs of the polymer films were punched out from the film and soaked into 15 mL of DMSO at room temperature (27 °C). The discs were taken out of the solvent after 24 h and their weights were measured after wipe-cleaning their surfaces with a lint-free paper. The percentage swelling of the discs was calculated using the expression [(Mw - Mo)/Mo] × 100, where Mo and Mw represent the disc masses in dry and wet conditions, respectively. After the swelling experiments, the discs were dried to constant weight and percent sol content was calculated using the expression [(Mo - Md)/Md] ×100 where Mo and Md represent the disc masses in pre and post swelling(dried) states.
In vitro degradation:
Degradation studies were conducted in NaOH solution (0.1 M). Sodium hydroxide degradation was used to screen the polymer degradation in a relatively short period of time. Disc-shaped polymer samples were weighed and placed in a small bottle containing 15 ml of NaOH. The bottle was incubated at 37 °C for certain periods of time. After incubation the films were washed with water and dried to a constant weight at 40 °C in vacuum. Weight loss percentage was calculated by comparing the initial mass (Wo) with the mass measured at a given time point (Wt), using the expression [(Wo-Wt)/Wo] ×100.
The FTIR spectra of all the synthesized pre-polymers (Fig 1) show a strong absorption band at around 1733 cm-1, which is characteristic absorptions of carbonyl stretching vibrations of ester groups and thus confirmed the formation of polyesters.6-8 The bands centered at around 2921 and 2851cm-1 were assigned to methylene (-CH2-) groups for the diacids/diols and observed in all the spectra of the polyesters.9 The broad stretch at 3404 and 3506 cm-1 was attributed to the stretching vibrations of the hydrogen-bonded carboxyl and hydroxyl groups.10,11 The characteristic absorption at around 1635 cm-1 corresponded to the alkenyl stretching (C=C bond) due to the presence of itaconic acid in the polymeric chain.12-14
The purified pre-polymers were characterized by 1H NMR. A proposed structural formula for the resulting copolyesters (Fig 2) showed the correlation between the different structural components and the observed chemical shifts of the pre-polymers. The multiple peaks around 2.8 ppm, and 4.1 ppm were attributed to the protons in –CH2–group and alcoholic –OH group from citric acid.2,5,7 The peak at around 3.6 ppm could be due to the proton signal of –OCH2CH2- from diol.2 The peaks at 0.9, 1.3 and 1.6 ppm were attributed to –CH2- protons of 1, 12-dodecanediol and 1,4-cyclohexanedimethanol with the peaks overlapping in [p(DDCI)]. The alkene peaks at around 5.8 and 6.2 ppm evidence the fact that the double bonds of itaconic acid were not involved in crosslinking. The absence of these peaks would have meant the double bonds were altered.
Tensile tests on the polymer films revealed the Young’s modulus (E) of the polymers [p(DDCI)] and [p(CHCI)] were 1.05 and 0.88 MPa respectively. The ultimate tensile strength was 0.27 and 0.87 for [p(DDCI)] and [p(CHCI)]. The % elongation at break was 80 % for [p(DDCI)] and 130 % for [p(CHCI)]. Crosslink density was 141 and 119 for [p(DDCI)] and [p(CHCI)] respectively. Figure 3 depicts the typical stress-strain curves of the synthesized polyesters. The increase in crosslink density of [p(DDCI)] could be due to the closer packing of the layers due to DD when compared to CHMD. Thus it is evident that the mechanical properties of the elastomers can be controlled by substituting different diol units. This difference in properties could be useful for a variety of biomedical applications. The Young’s modulus were closer to that of human thoracic aorta (0.60 MPa), elastin(1.1 MP) and myocardium of human (0.02-0.5 MPa).15,16
Thermal Analysis:
The thermal studies revealed that the elastomers were thermally stable. The DSC analysis of both the polyesters showed Tg below room temperature, a characteristic feature that determined their elastomer-like behavior.5 As shown in figure 4, the Tg of [p(DDCI)] (-0.63 °C) was lower than [p(CHCI)] (13.92 °C).
Swelling Experiments:
Equilibrium swelling was studied in DMSO which was chosen because of its high boiling point. The swelling experiments revealed that [p(DDCI)] and [p(CHCI)] swelled to 52.41% and 169 % of their original size respectively. The sol content of the polyester elastomers [p(DDCI)] and [p(CHCI)] was calculated as 3.17 % and 13.12 % respectively. The relatively small amount of the sol content confirmed the successful formation of polymer network. Although DMSO dissolved the pre-polymer, the final post-polymerized samples did not dissolve in DMSO even after soaking for several days. The low sol content indicated the very little presence of small oligomers trapped with the polymeric network. As the polymer-polymer intermolecular forces were high due to cross-linking and strong hydrogen bonding, the samples did not completely dissolve. This result was shown to be in agreement with the FTIR analysis which showed the presence of hydrogen bonded -OH and -COOH groups.5 The high swelling of the [p(CHCI)] in DMSO could be due to the weakening of the intermolecular interactions and disruption of physical cross links between the polymer chains. Also it could be due to lesser crosslink density than that of [p(DDCI)] polyester which had a more rigid network.
In vitro degradation:
Complete degradation of the polyesters was confirmed by degradation in the presence of 0.1 M NaOH. The polyester [p(DDCI)] degraded at a slower rate (i.e., took 24 h to degrade to 100%) when compared to [p(CHCI)], which degraded in a couple of hours. The polyester [p(DDCI)] displayed the slowest degradation rate due to the existence of longer hydrophobic chains of the diol and the higher crosslink density that did not allow molecules of the base to penetrate into the structure thus causing the cleavage of ester bonds. Thus it could be noted that the degradation rate of the polymer is tremendously influenced by the choice of the monomers.
CONCLUSIONS:
Two new biodegradable polyester elastomers, poly (1,12-dodecanediol citrate-co-1,12-dodecanediol itaconic acid) [p(DDCI)]; poly (1,4-cyclohexanedimethanol citrate-co-1,4-cyclohexanedimethanol itaconic acid) [p(CHCI)] were synthesized using melt condensation polymerization and thermal curing condition. The monomers were chosen because they were metabolic products in the body, their low cost and their availability from renewable sources. The mechanical and thermal properties of the polyesters showed that [p(DDCI)] had better cross-linking than that of [p(CHCI)]. Also, the glass transition temperature evidenced their elastomeric nature. The polymers had appreciable swelling characteristics which substantiate their cross-linking abilities. The Young’s modulus and crosslink density were higher for [p(DDCI)] while the degradation rates of [p(CHCI)] was higher. This was attributed to the structural difference between the two diols and the degree of crosslinking. Thus it is noticed that the choice of monomers (diols) can largely influence the physical properties of the elastomers so as to suit them for the requirements of various biomedical applications.
REFERENCES:
2. Yang J, Webb AR, Pickerill SJ, Hageman G and Ameer GA. Synthesis and evaluation of poly(diol citrate) biodegradable elastomers. Biomaterials. 27; 2006:1889-1898.
3. Tran RT, Zhang Y, Gyawali D and Yang J. Recent developments on citric acid derived biodegradable elastomers Recent Patents on Biomedical Engineering. 2; 2009: 216-227.
4. Pasupuleti S and Madras G. Synthesis and degradation of sorbital-based polymers. Journal of Applied Polymer Science. 121; 201: 2861-2869.
5. Djordjevic I, Choudhury NR, Dutta NK and Kumar S. Synthesis and characterization of novel citric acid-based polyester elastomers. Polymer. 50; 2009:1682-1691.
6. Song DK and Sung YK. Synthesis and characterization of biodegradable poly(1,4-butanediol succinate). Journal of Applied Polymer Science. 56: 1995: 1381–1395.
9. Brioude MM, Guimaraesa DH, Fiuza RDD, Prado LAS, Boaventura JS, Nadia JS and Josea NM. Synthesis and characterization of aliphatic polyesters from glycerol, by-product of biodiesel production, and adipic acid. Materials Research. 10(4); 2007: 335-339.
10. Xie D, Chen D, Jiang B and Yang C. Synthesis of novel compatibilizers and their application in PP/nylon-66 blends. I. Synthesis and characterization. Polymer. 41(10); 2000: 3599-3607.
11. Lee LY, Wu SC, Fu SS, Zeng SY, Leong WS and Tan LP. Biodegradable elastomer for soft tissue engineering. European Polymer Journal. 45(11); 2009: 3249-3256.
12. Shaker MA, Dore JJ and Younes HM. Synthesis, characterization and cytocompatibility of a poly(diol-tricarballylate) visible light photo-cross-linked biodegradable elastomer. Journal of Biomaterials Science, Polymer Edition. 21(4); 2010: 507-528.
13. Gyawali D, Nair P, Zhang Y, Tran RT, Zhang C, Samchukov M, Makarov M, Kim HK and Yang J. Citric acid-derived in situ crosslinkable biodegradable polymers for cell delivery. Biomaterials. 31(34); 2010: 9092-9105.
14. Kaihara S, Matsumura S and Fisher JP. European Journal of Pharmaceutics and Biopharmaceutics. 68(1); 2008: 67-73.
15. Gosline J, Lillie M, Carrington E, Guerette P, Ortlepp C and Savage K. Elastic proteins: biological roles and mechanical properties. Philosophical Transactions of the Royal Society B. 357(1418); 2002: 121-132.
16. Chen QZ, Bismarck A, Hansen U, Junaid S, Tran MQ, Harding SE, Ali NN and Boccaccini AR. Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue. Biomaterials. 29(1); 2008: 47-57.
Received on 18.12.2011 Modified on 31.12.2011
Accepted on 15.01.2012 © AJRC All right reserved
Asian J. Research Chem. 5(1): January 2012; Page 136-139