| Inhalable liposomes of low molecular weight heparin for the treatment of venous thromboembolism. | |
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MedLine Citation:
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PMID: 20845454 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study tests the feasibility of inhalable pegylated liposomal formulations of low molecular weight heparin (LMWH) for treatment of two clinical manifestations of vascular thromboembolism: deep vein thrombosis (DVT) and pulmonary embolism (PE). Conventional distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and long-circulating pegylated (DSPE-PEG-2000 and DSPE-PEG-5000) liposomes were prepared by hydration method. Formulations were evaluated for particle size, entrapment efficiency, stability, pulmonary absorption, anticoagulant, and thrombolytic effects in rats. Pulmonary absorption was monitored by measuring plasma antifactor Xa activity; anticoagulant and thrombolytic effects were studied by measuring reduction in thrombus weight and amount of dissolved radioactive clot in the blood, respectively. Pegylated liposomal were smaller and showed greater drug entrapment efficiency than conventional liposomes. All formulations produced an increase in pulmonary absorption and circulation time of LMWH upon first dosing. Three repeated dosings of conventional liposomes resulted in decreased half-life and bioavailability; no changes in these parameters were observed with pegylated liposomes. PEG-2000 liposomes were effective in reducing thrombus weight when administered every 48 h over 8 days. In terms of thrombolytic effects and dosing frequency, PEG-2000 liposomes administered via the pulmonary route at a dose of 100 U/kg were as effective as 50 U/kg LMWH administered subcutaneously. This paper suggests that inhalable pegylated liposomes of LMWH could be a potential noninvasive approach for DVT and PE treatment. |
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Authors:
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Shuhua Bai; Fakhrul Ahsan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 99 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-09-16 Completed Date: 2011-01-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 4554-64 Citation Subset: IM |
Copyright Information:
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© 2010 Wiley-Liss, Inc. and the American Pharmacists Association |
Affiliation:
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Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, Amarillo, Texas 79106, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Inhalation Animals Fibrinolytic Agents / administration & dosage*, therapeutic use* Heparin, Low-Molecular-Weight / administration & dosage*, therapeutic use* Liposomes / chemistry* Male Particle Size Polyethylene Glycols / chemistry Pulmonary Embolism / drug therapy* Rats Rats, Sprague-Dawley Venous Thromboembolism / drug therapy Venous Thrombosis / drug therapy* |
| Grant Support | |
ID/Acronym/Agency:
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R15 HL7713302/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fibrinolytic Agents; 0/Heparin, Low-Molecular-Weight; 0/Liposomes; 0/Polyethylene Glycols |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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