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 δlactone)s bearing distinct alkyl side groups were synthesized via ringopening copolymerization of ε-caprolactone and a small amount of various 5-alkyl δ-lactones using PEG as the macroinitiator and metalfree diphenyl phosphate as the catalyst. The analysis of 1 H 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.

Sustained Release of Nitric Oxide and Cascade Generation of Reactive Nitrogen/Oxygen Species via an Injectable Hydrogel for Tumor Synergistic Therapy

“…[ 65 ] The T gel 's of BK‐Gel and NO‐Gel were 35 °C and 34 °C, respectively. Consistent with previous studies, [ 52,53 ] the temperature‐responsive gelation of BK‐Gel/NO‐Gel should be ascribed to the formation of a percolated micelle network driven via micellar aggregation (Figure 3C,D; Figures S6 and S7, Supporting Information). Meanwhile, after modification with NEAA, NO‐PLGA‐PEG‐PLGA‐NO copolymers seemed to be more hydrophobic than PLGA‐PEG‐PLGA copolymers, which made NO‐micelles more prone to aggregate upon heating (Figure 3D), resulting in a 1 °C decrease in T gel of NO‐Gel.…”

“…First, the critical micelle concentrations (CMCs) of the two polymers were determined via the solubilization method of a hydrophobic probe, 1,6‐diphenyl‐1,3,5‐hexatriene (DPH). [ 52 ] The results showed that the two samples had a similar CMC (ca. 4.0 × 10 –4 g mL −1 ) at room temperature (Figure S5, Supporting Information).…”

“…The CMCs of PLGA‐PEG‐PLGA and NO‐PLGA‐PEG‐PLGA‐NO polymers were determined via the hydrophobic dye solubilization method. [ 52 ] Briefly, 30 µL DPH methanol solution (0.4 × 10 −3 m ) was added to 3 mL aqueous polymer solutions in the concentration range from 0.002 to 1 wt%. After equilibration at 4 °C overnight, the UV–vis spectra of the samples were recorded by a UV–vis spectrophotometer at room temperature.…”

“…[10,11] NO can down-regulate the expression of P-glycoprotein, a major drugresistant protein, to reverse multidrug resistance of tumor cells, solutions at or below ambient temperature but spontaneously convert into semi-solid physical hydrogels at body temperature by the body heat-induced sol-gel transition. [52][53][54] The sol state facilitates the encapsulation of drugs or cells. Upon injection into a target site, the hydrogel systems loaded with drugs or cells can be rapidly formed in situ, acting as reservoirs for continuous liberation of drugs or cell-growing matrices.…”

Intelligent Paper‐Free Sprayable Skin Mask Based on an In Situ Formed Janus Hydrogel of an Environmentally Friendly Polymer

“…This principle is applied to detect CMC. [ 39 ] According to Boltzmann fitting (Figure 3D), the addition of nicotinamide had no significant influence on the CMCs of the amphiphilic copolymer chains in water.…”