Decisive Influence of Hydrophobic Side Chains of Polyesters on Thermoinduced Gelation of Triblock Copolymer Aqueous Solutions

Abstract

A series of amphiphilic triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(ε-caprolactone-co-5-alkyl δ-lactone)s bearing distinct alkyl side groups were synthesized via ring-opening copolymerization of ε-caprolactone and a small amount of various 5-alkyl δ-lactones using PEG as the macroinitiator and metal-free diphenyl phosphate as the catalyst. The analysis of 1H NMR, GPC, DSC, and XRD confirmed that the synthetic copolymers had similar molecular weights and bulk properties; nevertheless, they exhibited quite different aqueous behaviors in response to temperature variations. While the polyesters without side chains simply presented a free-flowing sol over the entire examined temperature range, those bearing methyl or n-propyl side groups underwent a sol–gel transition upon heating and harvested a reversed thermosensitive hydrogel (T-Gel). Meanwhile, the sol–gel transition temperature of the polymer/water system could be easily tailored by adjusting the content of the n-propyl side group. In contrast, the polyesters containing longer n-amyl side groups formed a normal hydrogel (N-Gel) exhibiting a gel–sol (suspension) transition upon heating. Their different aqueous behaviors stemmed from the difference in the hydrophilic–hydrophobic equilibrium of the amphiphilic copolymers. The sol–gel transitions of the thermosensitive hydrogels were attributed to the aggregation of micelles and the dehydration of PEG. The copolymers bearing n-propyl side groups had good cytocompatibility and were fairly stable in a phosphate buffered saline for 80 days, whereas the formed thermosensitive hydrogel (20 wt %) was rapidly degraded via surface erosion within half a month after subcutaneous injection into mice. Consequently, this study indicates that subtle variation in the length of hydrophobic side chains plays a decisive role in the physical gelation of PEG/polyester copolymers. In addition, the thermosensitive hydrogels have the potential for drug and cell delivery based on their good biocompatibility and biodegradability.