ROS-responsive hydrogels with spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs for the repair of MRSA-infected wounds

For the treatment of MRSA-infected wounds,the spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs is a promising strategy.In this study,ROS-responsive HA-PBA/PVA(HPA)hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid(HA-PBA)and polyvinyl alcohol(PVA)to achieve spatiotemporally controlled release of two kinds of drug to treat MRSA-infected wound.The hydrophilic antibiotic moxifloxacin(M)was directly loaded in the hydrogel.And hydrophobic curcumin(Cur)with anti-inflammatory function was first mixed with Pluronic F127(PF)to form Cur-encapsulated PF micelles(Cur-PF),and then loaded into the HPA hydrogel.Due to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel,the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two drugs.In addition,the swelling,degradation,self-healing,antibacterial,anti-inflammatory,antioxidant property,and biocompatibility of hydrogels were tested.Finally,in the MRSA-infected mouse skin wound,the hydrogel-treated group showed faster wound closure,less inflammation and more collagen deposition.Immunofluorescence experiments further confirmed that the hydrogel promoted better repair by reducing inflammation(TNF-a)and promoting vascular(VEGF)regeneration.In conclusion,this HPA/M&CurPF hydrogel that can spatiotemporally sequential deliver antibacterial and anti-inflammatory drugs showed great potential for the repair of MRSA-infected skin wounds.