Combination and nanotechnology based pharmaceutical strategies for combating respiratory bacterial biofilm infections

Li Zhang, Hriday Bera, Hengzhuang Wang, Junwei Wang, Yi Guo, Changzhi Shi, Dongmei Cun, Claus Moser, Niels Høiby, Mingshi Yang


Respiratory infections are one of the major global health problems. Among them, chronic respiratory infections caused by biofilm formation are difficult to treat because of both drug tolerance and poor drug penetration into the complex biofilm structure. A major part of the current research on combating respiratory biofilm infections have been focused on destroying the matrix of extracellular polymeric substance and eDNA of the biofilm or promoting the penetration of antibiotics through the extracellular polymeric substance via delivery technologies in order to kill the bacteria inside. There are also experimental data showing that certain inhaled antibiotics with simple formulations can effectively penetrate EPS to kill surficially located bacteria and centrally located dormant bacteria or persisters. This article aims to review recent advances in the pharmaceutical strategies for combating respiratory biofilm infections with a focus on nanotechnology-based drug delivery approaches. The formation and characteristics of bacterial biofilm infections in the airway mucus are presented, which is followed by a brief review on the current clinical approaches to treat respiratory biofilm infections by surgical removal and antimicrobial therapy, and also the emerging clinical treatment approaches. The current combination of antibiotics and non-antibiotic adjuvants to combat respiratory biofilm infections are also discussed.

Original languageEnglish
Article number121507
JournalInternational Journal of Pharmaceutics
Publication statusPublished - 25 Mar 2022


  • Anti-Bacterial Agents/pharmacology
  • Bacterial Infections/drug therapy
  • Biofilms
  • Extracellular Polymeric Substance Matrix
  • Humans
  • Nanotechnology
  • Pharmaceutical Preparations
  • Respiratory Tract Infections/drug therapy
  • Inhalation therapy
  • aeruginosa
  • Antimicrobial therapy
  • Combination therapy
  • Biofilm infections
  • P
  • Nanotechnology-based drug delivery systems
  • Respiratory infections


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