Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route.

Abstract:

:Although heparin and low-molecular-weight heparins (LMWH) have been widely used clinically as anticoagulants, their broader use has been limited by the lack of noninvasive delivery methods for this class of molecules. In this study, we demonstrate an efficient, rapid, and reproducible delivery system for heparin through the lungs that is not confined to particles of a certain geometric or aerodynamic diameter. Importantly, blood levels after intrapulmonary administration of either heparin or LMWH were comparable to that of s.c. administration but are characterized by a more rapid onset of action (t(1/2) = 40 min vs. 2.5 h, respectively). Furthermore, we show in animal models, that inhaled heparin species efficiently inhibit diseases such as thrombosis and emphysema, and that the repetitive inhalation of formulated LMWH results in no observable toxicity from the delivery of reproducible systemic levels of heparin or LMWH.

authors

Qi Y,Zhao G,Liu D,Shriver Z,Sundaram M,Sengupta S,Venkataraman G,Langer R,Sasisekharan R

doi

10.1073/pnas.0402891101

keywords:

subject

Has Abstract

pub_date

2004-06-29 00:00:00

pages

9867-72

issue

26

eissn

0027-8424

issn

1091-6490

pii

101/26/9867

journal_volume

101

pub_type

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