Hybrid Hydrogel Networks by Photocrosslinking of Thermoresponsive alpha,omega-Itaconyl-PLGA-PEG-PLGA Micelles in Water: Influence of the Lithium Phenyl-2,4,6-Trimethylbenzoylphosphinate Photoinitinator

Abstract

Modification of thermogelling biodegradable copolymers with functional groups enables further covalent crosslinking of physical micelle-based hydrogels formed at specific temperature in water. The resulting hybrid hydrogel network exhibits an increase in stiffness and degradation stability. In this work, synthesized well-defined thermoresponsive alpha,omega-itaconyl-poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (alpha,omega-itaconyl-PLGA-PEG-PLGA) macromonomers with a high degree of itaconyl-substitution providing free double bonds are photocrosslinked in water at both 25 and 37 degrees C using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LiTPO) acting as water-soluble non-toxic photoinitiator. The effect of LiTPO on the thixotropic behavior of macromonomer in water at 25 degrees C without irradiation is evaluated. With the addition of a low amount of the photoinitiator (0.1 wt%), the degree of copolymer thixotropy increases. However, further increase in the photoinitiator concentration (0.5-3 wt%) leads to a lower degree of thixotropy. The photoinitiator is presumably interfering with the micellar self-assembly of the copolymer. This trend is also reflected in photocrosslinking efficiency, where the hybrid hydrogel networks with the highest storage moduli are achieved with very low concentrations of the photoinitiator (0.1 wt%) at 25 degrees C, while this trend is reversed at 37 degrees C. The hydrolytic stability of hydrogels prepared at 37 degrees C from 17 wt% macromonomer solution with 1% LiTPO exceeds 22 days.Modification of thermogelling biodegradable copolymers with functional groups enables further covalent crosslinking of physical micelle-based hydrogels formed at specific temperature in water. The resulting hybrid hydrogel network exhibits an increase in stiffness and degradation stability. In this work, synthesized well-defined thermoresponsive alpha,omega-itaconyl-poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (alpha,omega-itaconyl-PLGA-PEG-PLGA) macromonomers with a high degree of itaconyl-substitution providing free double bonds are photocrosslinked in water at both 25 and 37 degrees C using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LiTPO) acting as water-soluble non-toxic photoinitiator. The effect of LiTPO on the thixotropic behavior of macromonomer in water at 25 degrees C without irradiation is evaluated. With the addition of a low amount of the photoinitiator (0.1 wt%), the degree of copolymer thixotropy increases. However, further increase in the photoinitiator concentration (0.5-3 wt%) leads to a lower degree of thixotropy. The photoinitiator is presumably interfering with the micellar self-assembly of the copolymer. This trend is also reflected in photocrosslinking efficiency, where the hybrid hydrogel networks with the highest storage moduli are achieved with very low concentrations of the photoinitiator (0.1 wt%) at 25 degrees C, while this trend is reversed at 37 degrees C. The hydrolytic stability of hydrogels prepared at 37 degrees C from 17 wt% macromonomer solution with 1% LiTPO exceeds 22 days.