New biodegradable thermogelling copolymers having very low gelation concentrations.

New biodegradable multiblock amphiphilic and thermosensitive poly(ether ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] (PHB), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) blocks were synthesized, and their aqueous solutions were found to undergo a reversible sol-gel transition upon temperature change at very low copolymer concentrations. The multiblock poly(ether ester urethane)s were synthesized from diols of PHB, PEG, and PPG using 1,6-hexamethylene diisocyanate as a coupling reagent. The chemical structures and molecular characteristics of the copolymers were studied by GPC, 1H NMR, 13C NMR, and FTIR. The thermal stability of the poly(PEG/PPG/PHB urethane)s was studied by thermogravimetry analysis (TGA), and the PHB contents were calculated based on the thermal degradation profile. The results were in good agreement with those obtained from the 1H NMR measurements. The poly(PEG/PPG/ PHB urethane)s presented better thermal stability than the PHB precursors. The water soluble poly(ether ester urethane)s had very low critical micellization concentration (CMC). Aqueous solutions of the new poly(ether ester urethane)s underwent a sol-gel-sol transition as the temperature increased from 4 to 80 degrees C, and showed a very low critical gelation concentration (CGC) ranging from 2 to 5 wt %. As a result of its multiblock architecture, a novel associated micelle packing model can be proposed for the sol-gel transition for the copolymer gels of this system. The new material is thought to be a promising candidate for injectable drug systems that can be formulated at low temperatures and forms a gel depot in situ upon subcutaneous injection.