Bacterial Infection-microenvironment Responsive Polymeric Materials for the Treatment of Bacterial Infectious Diseases: a Review
WANG Yingjun1,2,3,4, HUANG Xuelian1,2, CHEN Junjian2,3, LIANG Yangbin1,2, XIONG Menghua1,2,3
1 School of Biomedical Science and Engineering, Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou International Campus, Guangzhou 510006 2 Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006 3 Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006 4 Key Laboratory of Biomedical Engineering of Guangdong Province, Guangzhou 510006
Abstract: Since the discovery of penicillin in 1928, the application of antibiotics has greatly reduced the morbidity and mortality of bacterial infectious di-seases, and numerous lives are survived from bacterial infection. However, with the widespread use and abuse of antibiotics, antimicrobial resistance has become a global public health issue. In addition, there are several problems that traditional antibiotic therapies encounter. Specifi-cally speaking, the antibiotics are rapidly metabolized and excreted from body after administration, only a few drugs reach the infected site and the bioavailability was low. In this case, high doses and long period treatments are required in clinical application, which lead to notable side effects. Besides, the poor therapeutic effect of antibiotics against biofilm infections and intracellular infections is also a pressing issue, leading to chronic infections and recurrent infections. In view of the problems existing in the traditional antibiotic delivery mode, the delivery of antibiotics by nanoparticles is proposed and shows great potential in the treatment of bacterial infection, which can improve the solubility of poorly soluble drugs, improve the pharmacokinetics and biodistribution of antibiotics, and overcome the tissue and cell barriers. Inspired by the fact that the physiological and physical microenvironment of bacterial infection sites is different from normal tissues, polymeric nanoparticles, that are responsive to the unique infectious microenvironments, have been developed to deliver antibiotics. These strategies remarkably improve the bioavailability and biodistribution of antibiotics, enhance the therapeutic efficacy of antibiotics against intracellular and biofilm infections, as well as attenuate the side effects. However, the delivery of antibiotics by nanoparticles shows limitations in the treatments of drug-resistant bacteria and especially for multidrug-resistant bacteria. Aiming at the problems of antibiotic resistance, antimicrobial peptides and their analogues have attracted extensive attention worldwide, since they exhibit broad-spectrum antibacterial activity with the less like-hood to develop drug resistance. Nevertheless, the cytotoxicity of these antibacterial agents hinders their clinical applications. For the sake of solving this problem, researchers designed responsive antimicrobial polymers that exhibited low toxicity in normal tissues, and transformed to active form to effectively kill drug-resistant bacteria when triggered by the acid infectious environment or bacterial enzymes in the infectious environment. In this review, we gave a brief introduction on the existing issues on traditional antimicrobial therapy, and an overview and current perspectives on the development infection-microenvironment responsive polymeric nanoparticles as carriers of antibiotics and the infection-responsive antimicrobial polymers for the treatment of bacterial infectious diseases over the past decade.
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2019, Vol. 33 
