Synthesis of a biodegradable polymer in gas expanded solution: effect of the process on cytocompatibility

Abstract

The aim of this study was to investigate the feasibility of eliminating organic solvent consumption for the synthesis of biodegradable poly(lactide ethylene oxide fumarate) (PLEOF). A gas expanded solution comprised of high pressure carbon dioxide (CO₂) and dichloromethane (DCM) or poly(ethylene glycol) (PEG) was used as an alternative medium for the synthesis of PLEOF. The effect of pressure (50–150 bar), temperature (25–50 °C) and the amount of DCM on the yield, molecular weight and thermal properties of PLEOF was examined. The results of ¹H NMR and ATR-FTIR analysis confirmed that it is possible to conduct the PLEOF synthesis in a high pressure CO₂ expanded solution as a reaction medium and acquire similar characteristics compared to the conventional method using neat DCM. A comparable yield was achieved in a high pressure CO₂ expanded solution process even when DCM was decreased to only 14% of the amount used in the conventional method. Increasing the pressure from 50 to 150 bar had no significant effect on the yield. In addition, DCM could be completely eliminated from the polymerisation by increasing the temperature to 50 °C and pressure to 100 bar. Under these conditions, the synthesis was carried out in PEG expanded solution due to the melting point depression effect of CO₂. It is, therefore, viable to conduct the polymerisation of PLEOF in gas expanded solution as a benign solvent and can either substantially reduce or eliminate the consumption of volatile organic solvents. The synthesised PLEOF was also crosslinked with poly(ethylene glycol) diacrylate (PEGDA) as a non-toxic crosslinker to produce an injectable hydrogel. The hydrogel prepared from PLEOF that was synthesised by gas expanded solution had better mechanical properties and less toxicity to primary human osteoblast cells. This study demonstrated that the synthesis process can have a significant impact on improving the physical properties and biological activity of the PLEOF polymer.