Document Detail


Inhalation treatment of pulmonary fibrosis by liposomal prostaglandin E2.
MedLine Citation:
PMID:  23228437     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Vera Ivanova; Olga B Garbuzenko; Kenneth R Reuhl; David C Reimer; Vitaly P Pozharov; Tamara Minko
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-08
Journal Detail:
Title:  European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V     Volume:  84     ISSN:  1873-3441     ISO Abbreviation:  Eur J Pharm Biopharm     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-31     Completed Date:  2014-01-30     Revised Date:  2014-10-16    
Medline Journal Info:
Nlm Unique ID:  9109778     Medline TA:  Eur J Pharm Biopharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  335-44     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Administration, Intravenous
Animals
Bleomycin / toxicity
Body Weight / drug effects
Dinoprostone / administration & dosage*
Disease Models, Animal
Hydroxyproline / metabolism
Idiopathic Pulmonary Fibrosis / chemically induced,  drug therapy*
Immunohistochemistry
Kidney / drug effects
Liposomes / administration & dosage,  metabolism
Liver / drug effects
Lung / drug effects,  metabolism
Mice
RNA, Messenger / metabolism
Spleen / drug effects
Time Factors
Tissue Distribution
Grant Support
ID/Acronym/Agency:
P-30 ES-005022/ES/NIEHS NIH HHS; R01 CA111766/CA/NCI NIH HHS; R01 CA111766/CA/NCI NIH HHS; R01 HL118312/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 0/RNA, Messenger; 11056-06-7/Bleomycin; K7Q1JQR04M/Dinoprostone; RMB44WO89X/Hydroxyproline
Comments/Corrections

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