title: Inhalable Andrographolide-β-cyclodextrin Inclusion Complexes for Treatment of Staphylococcus aureus Pneumonia by Regulating Immune Responses.
abstract: Bacterial pneumonia is a serious disease with high mortality if no appropriate and immediate therapy is available. Andrographolide (AG) is an anti-inflammatory agent extracted from a traditional Chinese herb andrographis paniculata. Oral AG tablets and pills are clinically applied for treatment of upper respiratory tract infections. However, the low solubility and bioavailability of AG lead to high doses and long-term therapy. Here we developed an andrographolide-β-cyclodextrin inclusion complex (AG-β-CD) for inhalation therapy of Staphylococcus aureus pneumonia. AG-β-CD was identified with X-ray diffraction and FT-IR. Surprisingly, both AG-β-CD and AG showed little in vitro anti-S. aureus activity. However, pulmonary delivery of AG, AG-β-CD, or penicillin had significant anti-S. aureus pneumonia effects. Leukocytes, neutrophils, white blood cells, total proteins, TNF-α, IL-6, NF-κB p65 expression, and bacterial colonies in the bronchoalveolar lavage fluids were detected. Pulmonary delivery of AG and AG-β-CD led to bacterial inhibition and inflammation alleviation by regulating immune responses, while penicillin only killed bacteria without significant immune regulation. Moreover, the antipneumonia activity of AG-β-CD was much higher than that of AG, probably resulting from locally accelerated AG dissolution due to β-CD inclusion. The aerodynamic diameter of AG-β-CD powders was 2.03 μm, suitable for pulmonary delivery. Inhalable AG-β-CD is a promising antibacterial and anti-inflammatory medicine for the treatment of S. aureus pneumonia by regulating immune responses, and the effect is enhanced by β-CD inclusion. AG and its formulations might be potent weapons against the resistant bacterial pneumonia due to their specific mechanism in the future.
authors.affiliation: Department of Graduates, Anhui Medical University , Hefei 230001, China.|Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine , Beijing 100850, China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Graduates, Anhui Medical University , Hefei 230001, China.|Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine , Beijing 100850, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine , Beijing 100850, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Graduates, Anhui Medical University , Hefei 230001, China.|Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine , Beijing 100850, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Pharmaceutical College of Henan University , Kaifeng 475004, China.
authors.forename: Erfeng
authors.initials: E
authors.lastname: Zhang
authors.affiliation: The First People's Hospital of Tancheng , Shandong 276199, China.
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Pharmaceutical College of Henan University , Kaifeng 475004, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Graduates, Anhui Medical University , Hefei 230001, China.|Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine , Beijing 100850, China.|Pharmaceutical College of Henan University , Kaifeng 475004, China.
authors.forename: Yiguang
authors.identifier: 0000-0002-3528-1397
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000627:therapeutic use*; D004224:Diterpenes / Q000737:chemistry* / Q000627:therapeutic use*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010406:Penicillins / Q000737:chemistry / Q000627:therapeutic use; D011014:Pneumonia / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D015850:Interleukin-6; D016328:NF-kappa B; D010406:Penicillins; D014409:Tumor Necrosis Factor-alpha; D047392:beta-Cyclodextrins; C030419:andrographolide
keywords: Staphylococcus aureus; andrographolide; bacterial pneumonia; cyclodextrin; immune regulation; inclusion complex; penicillin; pulmonary delivery