New Biodegradable Thermogelling Copolymers Having Very Low Gelation Concentrations

Abstract

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.

Polyhydroxyalkanoates: opening doors for a sustainable future

“…Our group reported the synthesis of multiblock amphiphilic and thermosensitive poly(ether ester urethane)s, which consist of PHB, PEG and PPG blocks (Figures 14a and b). 69 At PHB concentrations below 11.4 wt%, PHB/PEG/PPG poly(ether ester urethane)s were soluble in water and self-assembled into micelle formation with extremely low concentrations. When the concentration increased from 2 to 5 wt%, the PHB/PEG/PPG poly(ether ester urethane)s solution underwent sol-gel-sol transition as the temperature increased from 4 to 80°C.…”

“…The temperature-dependant sol-gel transition of the copolymer solution was attributed to the increased association of the micelles, which was caused by the multiple segments that link the micelles in a network-like gel structure. 69,70 The hydrolytic degradation of PHB/PEG/PPG poly(ether ester urethane) hydrogels was characterized by an initial incubation period, followed by the erosion of the polymer gel and the random chain scission of the ester bonds in PHB segments. 71 The relationship between the protein release and the hydrogel degradation process was also correlated.…”

Injectable Biodegradable Hydrogels

“…A thermosensitive and amphiphilic poly(ether ester urethane) multiblock copolymer consisting of PHB, PEG, and poly(propylene glycol) (PPG) (PEG/PPG/PHB) was synthesized. [47,48] This copolymer, in aqueous solutions and at very low concentrations (2-5 wt.-%). showed a sol-to-gel transition as a function of temperature change.…”

Synthetic routes to degradable copolymers deriving from the biosynthesized polyhydroxyalkanoates: A mini review

“…It showed a very low critical gelation concentration ranging from 2 to 5 wt%, much lower than that of the commercial thermogelling PEG-PPG-PEG triblock copolymers (15~20 wt% or above). Moreover, nonbiodegradable PEG-PPG-PEG triblock copolymers have been reported to show hyperlipidemia and high plasma level of cholesterol in rabbits and rats [92], and less cells (L929 mouse fibroblasts) attachment [93], suggesting that introducing a hydrophilic, biodegradable and biocompatible soft phase in the PHAs block copolymers is an effective way to design novel biomaterials. Other diisocyanate, including toluene diisocyanate [94], 2,2,4-trimethylhexamethylene diisocyanate [95][96][97], and L-lysine methyl ester diisocyanate [96][97][98] have also been applied to synthesize block copolymer.…”