A Temperature/pH Double-Responsive and Physical Double-Crosslinked Hydrogel Based on PLA and Histidine

Abstract

Hydrogel is a good drug carrier, widely used in the sustained-release aspect of tumor drugs, which can achieve the continuous release of drugs to the tumor sites. In this study, diethylene glycol monomethyl ether methacrylate (MEO2MA) and poly (ethylene glycol) methyl ether methacrylate (OEGMA) are temperature-sensitive monomers. N-Methacryloyl-L-Histidine (Mist) is pH sensitive monomer and ligand for metal coordination bond. The temperature-sensitive monomers and pH sensitive monomer with stereocomplex of modified polylactic acid (HEMA-PLLA30/PDLA30) were mixed, under 2,2’-azobis (2-methylpropionitrile) (AIBN) as radical initiator, polymer was formed by free-radical polymerization. The polymer was then immersed in ZnSO4 solution, the imidazole group of Mist monomer forms a tridentate metal coordination bond with Zn2+, temperature/pH double-responsive and physical double-crosslinked hydrogel was finally obtained. Comparing the hydrogen bond hydrogel, hydrogen bond and metal coordination bond double crosslinking hydrogel, metal coordination bond hydrogel, testing thermal stability, viscoelasticity, swelling, and morphology of three hydrogels. In addition, using UV-Visible spectroscopy (UV-Vis) to test the sustained release of the hydrophobic drug doxorubicin hydrochloride (DOX-HCl) in the human tumor environment (37 °C, pH = 5). We found that the temperature/pH double-responsive and physical double-crosslinked hydrogel had the most potential for the sustained drug release.

Photothermal Conversion of Hydrogel‐Based Biomaterial

“…Physical cross-linking of hydrogels occurs through the hydrophobicity of gel matrix molecular chains, [89] electrostatic interactions, hydrogen bonds, [90] and other mechanisms (Figure 6), forming water hydrogels in the form of microcrystals, micelles, helices, and entanglements. [91] It is reversible and can be controlled by changing conditions such as temperature, [92] ion concentration, [93] and pH [94] to adjust the formation and dissolution of the gel structure of biomaterials. The preparation of water hydrogels through physical cross-linking is simple, with strong water absorption performance and strong controllability.…”