Document Detail


Inhalable liposomes of low molecular weight heparin for the treatment of venous thromboembolism.
MedLine Citation:
PMID:  20845454     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shuhua Bai; Fakhrul Ahsan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  99     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4554-64     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc. and the American Pharmacists Association
Affiliation:
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, Amarillo, Texas 79106, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
R15 HL7713302/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Heparin, Low-Molecular-Weight; 0/Liposomes; 0/Polyethylene Glycols

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