Introduction: Ring opening polymerization (ROP) of macrolactones allows the formation of biopolyesters, such as poly(ω-pentadecalactone) [1], that share many similarities with polyethylene. ε-Decalactone, whose homopolymer is completely amorphous owing to the racemic stereochemistry of its butyl side chain, has found to be an excellent monomer to copolymerize with ω-PDL [2] and, therefore, reduce its high crystallization capability. However, in vitro degradation studies [3] demonstrated that, despite their increased amorphous character, these materials were very resistant to hydrolysis and can virtually be considered as non-biodegradable polymers. In this work, δ-hexalactone, a six-membered lactone with identical structure to δ-valerolactone but possesses a methyl pendant group, was employed in place of ε-DL trying to decrease the steric effect of the latter and increase the hydrophilicity of the copolymers.
Materials and Methods: Several copolymers based on ω-PDL and δ-HEX (Sigma Aldrich, assay >98%) were synthesized in bulk by one-pot one-step ROP using triphenyl bismuth as catalyst (obtained from Gelest). The molecular weights (Mw) of the copolymers increase proportionally with the ω-PDL content and range from 62 to 249 Kg mol-1. For proper evaluation, a poly(ω-pentadecalactone) homopolymer was also synthesized.
The poly(ω-pentadecalactone-co-δ-hexalactone) (with molar contents of δ-HEX from 18 to 61 %) were characterized by 1H and 13C NMR , GPC measurements and thermogravimetric analysis (TGA). Their crystallization behaviour and thermal properties were studied by means of differential scanning calorimetry (DSC) and Wide angle X-ray diffraction (WAXRD). In addition, films were prepared by pressure melting for mechanical testing with an Instron 5565 machine at room temperature (21ºC) and at body temperature (37ºC). Finally, an in vitro hydrolytic degradation study was also carried out at 37ºC for a period up to 26 weeks in phosphate buffered solution.
Results and Discussion: Figure 1 shows the progress of ln Mw against degradation time of the different copolymers of this study and the ω-PDL homopolymer, which did not lose molecular weight. The incorporation of δ-HEX units accelerated the hydrolysis and as a result, poly(ω-PDL-co-δ-HEX) exhibited degradation rates (KMw) values of between 0.0013 and 0.0019 days-1, that are higher than that of poly(ε-caprolactone) (0.0010 days-1).
Figure 1. ln Mw against degradation time of poly(ω-pentadecalactone-co-δ-hexalactone)
These materials, with a glass transition in the range of -35 to -43ºC and a melting point at temperatures between 55 and 90ºC, maintain their properties at body temperature, in contrast to other polyesters of high Tg (i.e. Polylactide, polyglycolide and their copolymers) or biopolymers of low Tm (<65ºC) such as PCL and its copolymers. Figure 2 shows typical stress-strain curves of the polymers at 21 ºC. As can be seen, the δ-HEX copolymers showed a marked improvement in flexibility compared to PPDL (and PCL) with lower secant modulus (from 26 to 179MPa for the copolymers and 300-350 MPa for both homopolymers). The polymers with ω-PDL contents higher than 72% present good ductility with strain at break values higher than 764%, while the rest of copolymers break earlier due to their reduced crystallinity degree and lower molecular weight.
Figure 2. Typical stress-strain curves of the poly(ω-pentadecalactone-co-δ-hexalactone)
Conclusion: The biodegradability, upgraded thermal stability, rapid crystallization from melt, proper processing with thermoplastic techniques of these copolyesters and their attractive mechanical properties (are stable at 21ºC and at 37ºC, present lower values of secant modulus than PCL and, therefore, a lower stiffness), make ω-pentadecalactone-co-δ-hexalactone copolymers very interesting substitutes for PCL in the biomedical field.
The authors are thankful for funds from the Basque Government, Department of Education, Universities and Research (GIC12/161-IT-632-13) and the Spanish Ministry of Innovation and Competitiveness MINECO (MAT2013-45559-P).
References:
[1] de Geus, M., van der Meulen, I., Goderis, B., van Hecke, K., Doschu, M., van der Werff, H., Koning, C.E., Heise, A. Performance polymers from renewable monomers: high molecular weight poly(pentadecalactone) for fiber applications. Polymer Chemistry 2010, 1, 525-533.
[2] Jasinska-Walc, L.; Bouyahyi M.; Rozanaski A.; Graf, R.; Hansen, M.R.; Duchateau, R. Synthetic Principles Determining Local Organization of Copolyesters Prepared from Lactones and Macrolactones. Macromolecules 2015, 48, 502-510.
[3] Fernandez, J.; Etxeberria, A.; Larrañaga Varga, A.; Sarasua, JR. Characterization of ω-pentadecalactone-co-ε-decalactone copolymers: Evaluation of thermal, mechanical and Biodegradation properties . Submitted to Macromolecular Rapid Communications 2015.