title: Tea tree oil nanoemulsions for inhalation therapies of bacterial and fungal pneumonia.
abstract: Tea tree oil (TTO) is a natural essential oil with strong antimicrobial efficacy and little drug resistance. However, the biomedical applications of TTO are limited due to its hydrophobicity and formulation problems. Here, we prepared an inhalable TTO nanoemulsion (nanoTTO) for local therapies of bacterial and fungal pneumonia. The optimal formulation of nanoTTOs consisted of TTO/Cremophor EL/water with a mean size of 12.5nm. The nanoTTOs showed strong in vitro antimicrobial activities on Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Candida albicans. After inhalation to the lung, the nanoTTOs had higher anti-fungal effect than fluconazole on the fungal pneumonia rat models with reduced lung injury, highly microbial clearance, blocking of leukocyte recruitment, and decrease of pro-inflammatory mediators. In the case of rat bacterial pneumonia, the nanoTTOs showed slightly lower therapeutic efficacy than penicillin though at a much lower dose. Taken together, our results show that the inhalable nanoTTOs are promising nanomedicines for local therapies of fungal and bacterial pneumonia with no obvious adverse events.
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China.
authors.forename: Boming
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Du
authors.affiliation: Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Beijing 100071, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jia
authors.affiliation: Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Beijing 100071, China. Electronic address: hanlicde@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China. Electronic address: jinyg@bmi.ac.cn.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000502:physiology; D000280:Administration, Inhalation; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D049329:Nanostructures / Q000737:chemistry; D008517:Phytotherapy / Q000379:methods; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects; D020947:Tea Tree Oil / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000891:Anti-Infective Agents, Local; D004655:Emulsions; D020947:Tea Tree Oil
keywords: Bacterial pneumonia; Fungal pneumonia; Nanoemulsion; Pulmonary delivery; Tea tree oil