title: Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats.
abstract: OBJECTIVE
  Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model.
  
  
  METHODS
  DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury.
  
  
  RESULTS
  The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models.
  
  
  CONCLUSIONS
  The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice.
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Chen
authors.forename: Shan-Mei
authors.initials: SM
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jin-Fu
authors.initials: JF
authors.lastname: Xu
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Yuan
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Teng
authors.forename: Rong-Xuan
authors.initials: RX
authors.lastname: Zhang
authors.forename: Dian-Hua
authors.initials: DH
authors.lastname: Jiang
authors.forename: Xavier
authors.initials: X
authors.lastname: Mulet
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Li
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001761:Bleomycin / Q000009:adverse effects; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D008081:Liposomes / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D058726:Nanoconjugates / Q000627:therapeutic use / Q000648:ultrastructure; D037662:Pulmonary Surfactant-Associated Protein A / Q000037:antagonists & inhibitors / Q000276:immunology; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000906:Antibodies; D008081:Liposomes; D058726:Nanoconjugates; D037662:Pulmonary Surfactant-Associated Protein A; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D003907:Dexamethasone