Hydrolytic stability of end-linked hydrogels from PLGA-PEG-PLGA macromonomers terminated by alpha,omega-itaconyl groups

摘要

Biodegradable amphiphilic PLGA-PEG-PLGA triblock copolymers end-terminated with itaconic acid (ITA) having reactive double bonds were synthesized by ring opening polymerization. The prepared alpha,omega-itaconyl-PLGA- PEG-PLGA telechelic macromonomers were additionally covalently crosslinked under an inert atmosphere by blue light irradiation without the use of a further cross-linker resulting in end-linked polymeric networks. The effects of the ITA amount attached to the alpha,omega-itaconyl-PLGA-PEG-PLGA copolymers and the crosslinking time on swelling behaviours and hydrolytic stability of the prepared well-defined polymeric network were investigated. Physicochemical properties were characterized by proton and carbon nuclear magnetic resonance spectroscopy (H-1 NMR, C-13 NMR), proton nuclear magnetic resonance relaxometry, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) and thermogravimetric analysis (TGA). It was found that the hydrolytic stability of ITA modified PLGA-PEG-PLGA end-linked hydrogels enhances with both increasing the time of crosslinking and the amount of double bonds attached to alpha,omega-itaconyl-PLGA-PEG-PLGA polymer chains. In comparison with the original un-crosslinked alpha,omega-itaconyl-PLGA-PEG-PLGA copolymer, the hydrolytic stability of the end-linked hydrogels significantly increased. Three kinds of water fractions (unbound, weakly and strongly bonded) were determined by proton NMR relaxometry in hydrogels containing 63 mol% of ITA crosslinked for 40 minutes. Even for hydrogels surviving 32 days in water the NMR relaxometry showed structural collapse of the hydrogel probably due to breaking of end-linked nodes followed by hydrolysis faster than water diffusion after day 15 of immersion. End-linked alpha,omega-itaconyl-PLGA- PEG-PLGA hydrogels can be used in medical, biological or tissue engineering applications.