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

A series of amphiphilic triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone-co-5-alkyl delta-lactone)s bearing distinct alkyl side groups were synthesized via ring-opening copolymerization of epsilon-caprolactone and a small amount of various 5-alkyl delta-lactones using PEG as the macroinitiator and metal-free diphenyl phosphate as the catalyst. The analysis of H-1 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.

Automated summary

A series of amphiphilic triblock copolymers composed of poly(ethylene glycol) and poly(epsilon-caprolactone-co-5-alkyl delta-lactone)s with distinct alkyl side groups were synthesized. These copolymers exhibited different aqueous behaviors in response to temperature variations, such as forming a reversed thermosensitive hydrogel or a normal hydrogel, depending on the length of hydrophobic side chains.