Suppression Effect Of Zn₂GeO₄:Cu²⁺-Loaded Microneedle Patches For Bacterial Infection

Pathogenic bacteria not only contaminate food,causing a great threat to food safety,but also often cause human and animal infection,seriously endangering life and health.Irrational use and even abuse of antibiotics result in the formation of drug resistance of pathogenic bacteria and the emergence of multi-drug bacteria and even superbugs.Methicillin-resistant Staphylococcus aureus（MRSA）is one of the typical superbugs.Conventional antibiotics are unable to effectively deal with the infection caused by drug-resistant bacteria.Hence,it is of great significance to develop new antibacterial materials that can combat resistant bacteria without causing drug resistance.In addition,bacteria often form biofilms at the site of infection and are difficult to eradicate.It is also important to use appropriate drug delivery methods to kill bacteria.Photodynamic sterilization based on photosensitizers and photocatalysts produces reactive oxygen species（ROS）to inactivate bacteria under in situ illumination of light with certain wavelength.Photodynamic sterilization does not cause bacteria resistance,but the depth of penetration of the light is limited.Some photosensitizers depending heavily on oxygen to generate singlet oxygen result in a hypoxic environment,which is detrimental to infectious wound healing.In this thesis,Zn₂GeO₄:Cu²⁺（ZGC）persistent luminescence nanorods with good ability to produce ROS after pre-illumination were synthesized and loaded onto the tips of dissolvable microneedles to prepare antibacterial microneedle patches（ZGC@MNs）for the therapy of MRSA infected wound.The main results are as follows:ZGC nanorods with good persistent luminescence life were synthesized by regulating the doped amount of Cu²⁺,pH and hydrothermal time.The synthesized ZGC nanorods emitted green phosphorescence with the emission peak at 537 nm under the excitation of 254 nm UV light.After 1 h of excitation,ZGC could maintain luminescence for more than 24 h and the ROS of singlet oxygen,hydroxyl radical and superoxide radical could be produced for more than 48 h.The amount of ROS produced by ZGC was concentration-dependent,and the rate of ROS generation was positively correlated with the time of pre-illumination.The possible mechanism of the persistent luminescence and ROS production of ZGC after excitation was discussed by using the conduction band-valence band model.The antibacterial performance of ZGC with and without pre-illumination was compared.ZGC with pre-illumination possessed better antibacterial performance owning to ROS production.Treatment with 250μg m L^-1 of ZGC with pre-illumination severely killed MRSA with 2.65-log reduction of viability.ZGC also displayed low cytotoxicity and good hemolysis compatibility for the prospect of biomedical application.These researches provided a sound basis for the wide application of persistent luminescence nanomaterials in antibacterial treatment.ZGC dispersed in soluble sodium hyaluronate was loaded into the tips of microneedles with polyvinyl alcohol as backing layer via a mold method to prepare ZGC@MNs patches.The mechanical strength of tips introduced with 9 mg m L^-1 of ZGC in Na HA solution was the best,and tips were strong enough to penetrate the skin and dissolve to release ZGC in 10 min.ZGC@MNs with pre-illumination exhibited obvious antibacterial effect in vitro.The application of ZGC@MNs with pre-illumination to BALB/c mice bearing MRSA infected wounds could improve the infected wound,reduce the degree of inflammation,and promote wound healing.No obvious changes in body weight and organ lesions were observed in the mice during the therapy,indicating that ZGC@MNs had no obvious toxic and side effects.ZGC@MNs provides a new therapeutic platform for bacterial infections of wounds.