Responsive Multilayer And Hydrogel Based Drug For Resisting Bacterial Infection

The bacterial colonization and adhesion on biomedical implants and subsequent biofilm formation often lead to serious bacterial infections.The sudden rise in antibiotic-resistant bacterial infections is the main reason for life-threatening infection diseases.Currently,intravenous antibiotic injection is the most practicing way to deal with implant-associated infections.However,the occurrence of antibiotic-resistant bacteria has become more dangerous by misuse and taking a huge amount of antibiotics,which further poses a serious threat to human health.To overcome these obstacles,many efforts have been devoted to developing an intelligent drug releasing system,which can release the drugs by responding to internal or external stimulations.Such multifunctional devices are innovative medical approaches capable of targeting the drug and their therapy.In this study,a pH and HAase dual-responsive multilayer and a NIR respesive hydrogel with both controlled drug delivery properties have been successfully constructed,and their intelligent antibacterial behaviors were investigated.An antibacterial drug-controlled release multilayer surface based on a layer-by-layer(LBL)assembly of polyacrylic acid(PAA)and chitosan quaternary ammonium salt(QCS)was developed.Gentamicin sulfate(GS)is incorporated into the multilayer and hyaluronic acid(HA)is electrostatically adsorbed on the topmost layer as a sealing layer.The prepared surface showed promising antibacterial performance against E.coli and S.aureuswith antibacterial efficiency higher than 99%.During the bacteria infection occurred,the pH of the infected microenvironment slightly increases,leading to the swelling of the multilayer.Meanwhile,the HAase secreted by the bacteriadegradesthe HA layer and further accelerate the in response-controlled drug release and kills bacteria.The outermost HA layer provides good stability to multilayer surface in the absence of bacteria.It is believed that the pH and HAase based controlled drug delivery system with excellent antibacterial activity could be a new promising surface for infection resistance medical devices.An hydrogel with controlleddrug releasing performance and photothermal effect,which relies on a stable exogenous stimulus,was fabricated.HPAE polymer was synthesized byMichael addition among pentaerythritol triacrylate(PETA),polyethylene glycol diacrylate(PEGDA)and dopamine,and the HPAE-Py polymer was obtained by covalently linking pyrrole on the endof PETA and PEGDA moiety of the HPAE.Both of the HPAE and HPAE-Py polymer were obtained sucessfully as confirmed by NMR and FT-IR anaylsis.Thehydrogel is constructed based on the crosslinking among HPAE-Py chains and silk fibroinbyFe3+triggered polymerization ofPpy nanoparticlesandcatechol-Fe3+ complexation.The GS drugs were simultaneous loaded in the hydrogels during the hydrogel formation.Gelation time,swelling rates as well as the drug releaseing behavior were investigated.The results showed that the polymer with a mass ratio of 40%HPAE-Py in the mixture resulted in the fastest gelation(2 mins)and 35%GS was released in 4 h.Due to the existence of Ppy nanoparticles,the hydrogel showed a high photothermal effect with the temperature increased 80℃ after 1 5 min irridiation.Antibacterial tests also showed that thehydrogels exhibit much more higher bactericidal efficiency against E.coli.and S.aureusunder the NIR irradiation.The results demonstrated that the prepared hydrogel proven to be promising carriers for synergistic chemotherapy and photothermal therapy.