Pulmonary delivery of tea tree oil-β-cyclodextrin inclusion complexes for the treatment of fungal and bacterial pneumonia

J Pharm Pharmacol. 2017 Nov;69(11):1458-1467. doi: 10.1111/jphp.12788. Epub 2017 Aug 15.


Objectives: Bacterial pneumonia is a common cause of death worldwide. Tea tree oil (TTO) is a potent antimicrobial natural product, which is formulated in dry powder inhalers (DPIs) for the treatment of fungal and bacterial pneumonia.

Methods: Tea tree oil-β-cyclodextrin inclusion complexes (TTO-β-CD) were prepared and characterized. Aerodynamic properties of TTO-β-CD powders were measured. The rat models of fungal (Candida albicans) and bacterial (Acinetobacter baumannii) pneumonia were prepared. Saline, TTO, TTO-β-CD and the positive drug (fluconazole or penicillin) were directly delivered to the rat lungs. Pathological and biological assays were conducted.

Key findings: Tea tree oil-β-CD powders had an appropriate aerodynamic diameter of 5.59 μm and the fine particle fraction of 51.22%, suitable for pulmonary delivery. TTO-β-CD showed higher and similar antipneumonic effects on the rat models than fluconazole and penicillin, respectively. The effects of TTO-β-CD were higher than TTO alone. The antipneumonic mechanisms involved blocking the recruitment of leucocytes and neutrophils, eliminating the microbes, downregulating pro-inflammatory cytokines (including tumour necrosis factor-α, interleukin-1β and interleukin-6), suppressing cyclooxygenase 2 expression, and further reducing lung injury.

Conclusions: Inhaled TTO-β-CD powders have the advantages of portability, high stability, self-administration, high lung deposition and good antipneumonic effect. It is a promising DPI for the treatment of fungal and bacterial pneumonia.

Keywords: bacterial pneumonia; cyclodextrin; fungal pneumonia; pulmonary delivery; tea tree oil.

Publication types

  • Comparative Study

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / isolation & purification
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / pharmacology
  • Candida albicans / isolation & purification
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Fluconazole / pharmacology
  • Lung / metabolism
  • Lung / microbiology
  • Male
  • Penicillins / pharmacology
  • Pneumonia / drug therapy
  • Pneumonia / microbiology
  • Pneumonia, Bacterial / drug therapy
  • Pneumonia, Bacterial / microbiology
  • Rats
  • Rats, Sprague-Dawley
  • Tea Tree Oil / administration & dosage*
  • Tea Tree Oil / pharmacokinetics
  • Tea Tree Oil / pharmacology
  • Tissue Distribution
  • beta-Cyclodextrins / chemistry


  • Anti-Bacterial Agents
  • Antifungal Agents
  • Penicillins
  • beta-Cyclodextrins
  • Tea Tree Oil
  • Fluconazole
  • betadex