Gelatinase-responsive biodegradable targeted microneedle patch for abscess wound treatment of S. aureus infection

• Published in: International journal of biological macromolecules 2023-12, Vol.253, p.127548-127548, Article 127548
• Main Authors: Lei, Xiao-Ling, Cheng, Kai, Hu, Yong-Guo, Li, Yong, Hou, Xiao-Lin, Zhang, Fang, Tan, Lin-Fang, Zhong, Zi-Tao, Wang, Jian-Hao, Fan, Jin-Xuan, Zhao, Yuan-Di
• Format: Article
• Language: English
• Subjects: Abscess wound; Biodegradable microneedle; Photodynamic therapy
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.127548

Abscess wound caused by bacterial infection is usually difficult to heal, thus greatly affect people's quality of life. In this study, a biodegradable drug-loaded microneedle patch (MN) is designed for targeted eradication of S. aureus infection and repair of abscess wound. Firstly, the bacterial responsive composite nanoparticle (Ce6@GNP-Van) with a size of about 182.6 nm is constructed by loading the photosensitizer Ce6 into gelatin nanoparticle (GNP) and coupling vancomycin (Van), which can specifically target S. aureus and effectively shield the phototoxicity of photosensitizer during delivery. When Ce6@GNP-Van is targeted and enriched in the infected regions, the gelatinase secreted by the bacteria can degrade GNP in situ and release Ce6, which can kill the bacteria by generating ROS under laser irradiation. In vivo experiments show that the microneedle is basically degraded in 10 min after inserting into skin, and the abscess wound is completely healed within 13 d after applying Ce6@GNP-Van-loaded MN patch to the abscess wound of the bacterial infected mice with laser irradiation, which can simultaneously achieve the eradication of biofilm and subsequent wound healing cascade activation, showing excellent synergistic antibacterial effect. In conclusion, this work establishes a synergistic treatment strategy to facilitate the repair of chronic abscess wound. The biodegradable MN patch is loaded with enzyme-responsive antimicrobial nanoparticle Ce6@GNP-Van was developed in this study for eradicating traumatic bacterial infection and promoting stalled healing of abscess wound. The responsive MN system has the following features: (1) the MN patch can physically penetrate and disrupt the bacterial biofilm structure after being applied to the infected site to facilitate the release of the antimicrobial agent; (2) the loading of Ce6 into GNP nanoparticle significantly inhibits the ability of singlet oxygen production and avoids phototoxicity during delivery; (3) Ce6@GNP-Van can target the bacterial community and release the drug only in response to the gelatinase secreted by the bacterial community, and generate a large amount of ROS under laser irradiation, which enhances the specific killing to bacteria by the nanoparticle and thus promotes the wound repairation. The experimental results show that the combination of antimicrobial therapy and MN drug delivery system can meet the requirements of precise targeting of bacteria and stimulation of responsive dr