Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats

• Published in: PloS one 2013-03, Vol.8 (3), p.e58275
• Main Authors: Chen, Xue-Yuan, Wang, Shan-Mei, Li, Nan, Hu, Yang, Zhang, Yuan, Xu, Jin-Fu, Li, Xia, Ren, Jie, Su, Bo, Yuan, Wei-Zhong, Teng, Xin-Rong, Zhang, Rong-Xuan, Jiang, Dian-Hua, Mulet, Xavier, Li, Hui-Ping
• Format: Article
• Language: English
• Subjects: Adult respiratory distress syndrome; Animal models; Animals; Antibodies; Antibodies - immunology; Biology; Bleomycin; Bleomycin - adverse effects; Bronchoalveolar Lavage Fluid - immunology; Bronchoalveolar Lavage Fluid - microbiology; Central nervous system depressants; Current distribution; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - pharmacology; Disease Models, Animal; Drug dosages; Extrusion; Glucocorticoids; Health aspects; Hospitals; Inflammation; Injuries; Kidneys; Laboratory animals; Lipids; Liposomes; Liposomes - ultrastructure; Liver; Lung - drug effects; Lung - pathology; Lung diseases; Lung Injury - chemically induced; Lung Injury - drug therapy; Lung Injury - mortality; Lung Injury - pathology; Lungs; Male; Materials Science; Medical treatment; Medicine; Morbidity; Nanoconjugates - therapeutic use; Nanoconjugates - ultrastructure; Pathogenesis; Pathology; Protein A; Proteins; Pulmonary fibrosis; Pulmonary Surfactant-Associated Protein A - antagonists & inhibitors; Pulmonary Surfactant-Associated Protein A - immunology; Rats; Respiratory distress syndrome; Respiratory system agents; Rodents; Spleen; Steroids; Steroids (Organic compounds); Stress concentration; Surface active agents; Surfactant protein A; Surfactants; Transforming Growth Factor beta1 - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0058275

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. 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. 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. 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.