title: Inhalation treatment of pulmonary fibrosis by liposomal prostaglandin E2.
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. We hypothesized that the local pulmonary delivery of prostaglandin E2 (PGE2) by liposomes can be used for the effective treatment of IPF. To test this hypothesis, we used a murine model of bleomycin-induced IPF to evaluate liposomal delivery of PGE2 topically to the lungs. Animal survival, body weight, hydroxyproline content in the lungs, lung histology, mRNA, and protein expression were studied. After inhalation delivery, liposomes accumulated predominately in the lungs. In contrast, intravenous administration led to the accumulation of liposomes mainly in kidney, liver, and spleen. Liposomal PGE2 prevented the disturbances in the expression of many genes associated with the development of IPF, substantially restricted inflammation and fibrotic injury in the lung tissues, prevented decrease in body weight, limited hydroxyproline accumulation in the lungs, and virtually eliminated mortality of animals after intratracheal instillation of bleomycin. In summary, our data provide evidence that pulmonary fibrosis can be effectively treated by the inhalation administration of liposomal form of PGE2 into the lungs. The results of the present investigations make the liposomal form of PGE2 an attractive drug for the effective inhalation treatment of idiopathic pulmonary fibrosis.
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Ivanova
authors.forename: Olga B
authors.initials: OB
authors.lastname: Garbuzenko
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Reuhl
authors.forename: David C
authors.initials: DC
authors.lastname: Reimer
authors.forename: Vitaly P
authors.initials: VP
authors.lastname: Pozharov
authors.forename: Tamara
authors.initials: T
authors.lastname: Minko
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D015232:Dinoprostone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000378:metabolism; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000187:drug effects; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D012333:RNA, Messenger; D001761:Bleomycin; D015232:Dinoprostone; D006909:Hydroxyproline