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

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.