Temperature-sensitive multifunctional intelligent responsive hydrogel based on carboxymethyl agarose and N-isopropylacrylamide: Controlled drug release and accelerated wound healing

Abstract

Wound healing remains challenging due to posttraumatic pain. At present, most wound dressings ignore the importance of wound pain. In this study, a temperature-sensitive multifunctional intelligent hydrogel patch (CPAG) containing lidocaine has developed for wound healing. CPAG hydrogel was prepared by grafting N-isopropylacrylamide and acrylamide onto carboxymethyl agarose (CMA) modified by agarose and encapsulating gallic acid and lidocaine. FTIR, 1H NMR spectroscopy, SEM and rheology were used to investigate its structure and temperature-sensitive properties. The contraction force generated by the temperature response characteristics of CPAG at 30 °C can accelerate wound healing. In vitro release assays demonstrated that CPAG directly controlled the same amount of lidocaine release at different temperatures through the competition between polymer-polymer and polymer-water interactions. In addition, MTT, H&E staining and stimulation test further proved its biological safety. The pain behavior study showed that the pain inhibition rates of the lidocaine cataplasms and LID@CPAG were 51.16 % and 67.83 %, respectively. In vitro and in vivo studies have shown that compared with the blank group, the bleeding volume of LID@CPAG decreased by 54.3 %, and the wound healing rate reached 97 %. CPAG hydrogel can play a comprehensive therapeutic role in accelerating wound closure by controlling drug release, analgesia, antioxidation and hemostasis.