Spatiotemporally responsive cascade bilayer microneedles integrating local glucose depletion and sustained nitric oxide release for accelerated diabetic wound healing  

作　　者：Yongnian Zeng Chenyuan Wang Jiapeng Lei Xue Jiang Kai Lei Yinli Jin Tianshu Hao Wen Zhang Jianying Huang Wei Li 

机构地区：[1]Department of Thyroid and Breast Surgery,Zhongnan Hospital of Wuhan University,School of Pharmaceutical Sciences,Wuhan University,Wuhan 430071,China [2]Clinical Trial Center of Zhongnan Hospital,Wuhan University,Wuhan 430071,China [3]Tumor Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center,Wuhan 430071,China [4]TaiKang Center for Life and Medical Sciences,Wuhan University,Wuhan 430071,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第11期5037-5052,共16页药学学报（英文版）

基　　金：National Natural Science Foundation of China(NSFC,Nos.82373798,52103182);the Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China(project No.2020ZX09201007);Innovation Transformation Research Project of Zhongnan Hospital of Wuhan University(project No.YXCXZH2024003,China).

摘　　要：High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing via local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating l-arginine (Arg)-loaded nanoparticles (NPs). After wound administration, the base part rapidly dissolved, resulting in prompt separation of the MN tip within the wound tissue, which subsequently responded to the overexpressed matrix metalloproteinase-9 (MMP-9) in diabetic lesions, leading to the responsive release of GOx. The released enzyme catalyzed glucose into gluconic acid and hydrogen peroxide (H_(2)O_(2)), which not only reduced glucose level within the diabetic wound, but also initiated the cascade reaction between H_(2)O_(2) with the Arg that was released from NPs, thereby achieving continuous production of NO for 7 days. Our findings demonstrate that a single administration of the MN patch could effectively heal non-infected or biofilm-infected diabetic wounds with the multifunctional properties.

关 键 词：MICRONEEDLE Wound healing DRUGDELIVERY Sustained release Nitric oxide Glucosedepletion Glucose oxidase Nanoparticles 

分 类 号：R587.1[医药卫生—内分泌] R318[医药卫生—内科学]