Infectious diseases, especially multidrug-resistant bacterial infections, have caused crises and majorly disrupted public health and economic stability worldwide. Many natural essential oils, especially tea tree oil, have potential to treat multidrug-resistant bacteria, such as H. pylori and P. aeruginosa. However, there are some problems need to be solved, such as poor stability upon light or oxygen exposure. Therefore, it is urgent to develop the ideal formation to tackle these difficulties. Herein, we reported the novel chitosan-modified self-nanoemulsion (TNE) encapsulating natural essential tea tree oil with strong antibacterial and stability characterize. In this study, we found that this self-nanoemulsion (size: 212 nm, PDI: 0.124, zeta potential: −20.5 mV, 6 % tea tree oil) not only had physical properties, good stability and tissue safety, but also had better antibacterial synergism (2–8 times) than that of water suspension against various multidrug-resistant bacterial (such as H. pylori, MRSA and P. aeruginosa). Additionally, TNE showed high antibacterial effectiveness in vivo, reduced inflammation, promoted ulcer healing after H. pylori infection and accelerated wound healing after P. aeruginosa infection. Importantly, this novel self-nanoemulsion can induce 274 protein down-regulated and 251 protein up-regulated, and disrupt H. pylori metabolic processes (glyoxylate, dicarboxylic acid, glutamate and tryptophan metabolism) and reduced its viability, leading to significant synergistic antibacterial effects. TNE is a potential treatment for skin wounds or ulcers caused by multidrug-resistant bacterial infections.
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