Smart hydrogels have received increasing attention for their great potential for the applications in many fields. Herein, we report a facile approach to prepare a class of dual-responsive hydrogels assembled from synthetic statistical/block thermal-responsive copoly（L-glutamate）s copolymerized with poly（ethylene glycol）, which were prepared by ring-opening polymerization（ROP） and post-modification strategy. The incorporation of oligo（ethylene glycol）（OEG） and glutamic acid residues offers the gels with thermal-and p H-responsive properties simultaneously. We have systematically studied the influence of both temperature and p H on the gelation behaviors of these copolymers. It is found that the increase of glutamic acid content and solution p H values can significantly suppress the gelation ability of the samples. Circular dichroism（CD） results show that the α-helix conformation appears to be the dominant secondary conformation. More interestingly, the gelation property of the block copolymer with statistical thermal-responsive copoly（L-glutamate）s shows greater dependence on p H as compared to that with block segments due to the distinct morphology of the self-assemblies. The obtained hydrogels exhibit p H-dependent and thermal-responsive gelation behaviors, which enable them as an ideal smart hydrogel system for biomedical applications.
A series of ABA triblock copolymers of poly(?-(2-methoxy ethoxy)esteryl-glutamate)-block-poly(ethylene glycol)-blockpoly(?-(2-methoxy ethoxy)esteryl-glutamate) with poly(ethylene glycol) as middle hydrophilic B block and oligo(ethylene glycol)-functionalized polyglutamate(poly-L-EG2Glu) as terminal A blocks were prepared via ring-opening polymerization of EG2 Glu N-carboxyanhydride(NCA). The resulting P(EG2Glu)-b-PEG-b-P(EG2Glu) triblocks can spontaneously form hydrogels in water. The intermolecular hydrogen bonding interactions between polypeptides blocks were responsible for the formation of gel network structure. These hydrogels displayed shear-thinning and rapid recovery properties, which endowed them potential application as injectable drug delivery system. The mechanical strength of hydrogels can be modulated by copolymer composition, molecular weight and concentrations. Also, it was found that the hydrogels' strength decreased with temperature due to dehydration of polypeptide segments. Atomic force microscopy and scanning electron microscopy images revealed that these hydrogels were formed through micelle packing mechanism. Circular dichroism and Fourier transform infrared spectroscopy characterizations suggested the poly-L-EG2 Glu block adopted mixed conformation. A preliminary assessment of drug release in vitro demonstrated the hydrogels can offer a sustained release of doxorubicin(DOX) and the release rate could be controlled by varying chemical composition.
We investigated the ring opening polymerization （ROP） of di- and tri-ethylene glycol monomethyl ether functionalized L-glutamate N-carboxyanhydrides （NCAs） using hexamethyldisilazane （HMDS） as primary initiator and 1,5,7-triazabicyclo-[4.4.0]dec-5-ene （TBD） as co-initiator. The binary initiator system afforded a living ROP for these pegylated NCAs, and a series of homopolypeptides with controlled molecular weight （MW） and low polydispersity were obtained. We then systematically studied the helical content and clouding point （CP） dependence on polypeptide MW using circular dichroism （CD） spectroscopy and turbidity measurements, respectively. We found that the helical content of both homopolypeptides increased with MW, but the triethylene glycol functionalized poly-L-glutamate （poly-L-EG3Glu） intended to form more stable or-helical structure than diethylene glycol functionalized counterpart （poly-L-EG2Glu） at similar MW. Accordingly, the CP of poly-L-EG2Glu with known end group has strong dependence on its helical content, which is essentially determined by MW. Our results suggested that the thermal responsive properties of these unique pegylated poly- L-glutamates not only rely on their chemical structure but also on their secondary structures, wh^ch is different from conventional thermal responsive polymers.
A series of monomethoxy poly（ethylene glycol） （mPEG） grafted copolyglutamates （PmPEGs） were synthesized through ring-opening polymerization （ROP） followed by click chemistry. Supramolecular hydrogels based on polymer inclusion complexes （ICs） between PmPEG and α-cyclodextriri （α-CD） were prepared in aqueous solution. The rheological measurements indicated their gelation properties were affected by several factors including the mPEG length, graft density and the sample concentration. These hydrogels displayed thermo-sensitive gel-sol transition under appropriate conditions due to the reversible mPEG and α-CD inclusion complexation. These hydrogels also showed pH-sensitive behavior due to the deprotonate of carboxylic acid side groups. The ICs formation of a channel-type crystalline structure induced gelation mechanism was verified by various techniques. In vitro cytotoxicity assays demonstrated that the supramolecular hydrogels are nontoxic and cytocompatible.
