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

Proceedings of the National Academy of Sciences of the United States of America
Yiwei QiRam Sasisekharan

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.

References

Mar 1, 1976·Thrombosis Research·A N TeienU Abildgaard
Jun 20, 1997·Science·D A EdwardsR Langer
Aug 1, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·A Leone-BayN Santiago
Aug 4, 1998·Journal of Applied Physiology·D A EdwardsR Langer
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·G A AmeerR Langer
Dec 4, 1994·Journal of Aerosol Medicine : the Official Journal of the International Society for Aerosols in Medicine·D Köhler
Mar 14, 2000·Respiratory Medicine·K E Bendstrup, J I Jensen
Mar 17, 2000·Pulmonary Pharmacology & Therapeutics·Z Diamant, C P Page
Mar 29, 2002·Journal of Pharmaceutical Sciences·Yuyan JiaoPhilippe Maincent
May 10, 2002·The European Respiratory Journal·K E BendstrupJ I Jensen
Jul 13, 2002·Journal of Pharmaceutical Sciences·John ArnoldDennis J Pillion
Sep 5, 2002·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Eric S HayesMichael J A Walker
Sep 21, 2002·Pharmaceutical Research·Dmitry MalkovIsabel Gomez-Orellana
Jan 9, 2003·Expert Opinion on Pharmacotherapy·Geno J Merli
Jan 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Mallik SundaramRam Sasisekharan
Feb 26, 2003·Cell·Mirna Perez-MorenoElaine Fuchs
Mar 4, 2003·Nature Reviews. Molecular Cell Biology·Karl Matter, Maria S Balda
Mar 6, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Bogdan I FloreaGerrit Borchard

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Citations

Nov 4, 2011·Applied Microbiology and Biotechnology·Ujjwal BhaskarRobert J Linhardt
Mar 7, 2012·Applied Microbiology and Biotechnology·C K M TripathiVikas Mishra
Nov 28, 2007·Pharmaceutical Research·Reinhard Vehring
Jun 26, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Kamrun NaharFakhrul Ahsan
Jan 30, 2010·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Philipp MarkartAndreas Guenther
Nov 30, 2013·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Brijeshkumar PatelFakhrul Ahsan
Jun 5, 2013·Expert Opinion on Drug Delivery·Hui Xin OngPaul M Young
Nov 28, 2015·Expert Opinion on Drug Delivery·Jooho Park, Youngro Byun
Jul 22, 2015·Journal of Veterinary Emergency and Critical Care·Jill S ManionKari V Lunsford
Jul 28, 2012·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Yasmine A GomaaRyan F Donnelly
Jan 13, 2016·Biological & Pharmaceutical Bulletin·Ayumu AsaiHirokazu Okamoto
Jul 21, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Shuhua BaiFakhrul Ahsan
Oct 11, 2008·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·C I GraingerB Forbes
Mar 11, 2011·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Thiagavathi S Ramyaa LakshmiMary Babu
Jun 17, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Nusrat A Motlekar, Bi-Botti C Youan
Apr 1, 2005·Drug Discovery Today. Technologies·Rita Vanbever
Jun 9, 2005·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Ben Forbes, Carsten Ehrhardt
Aug 29, 2013·ISRN Pharmacology·Clive Page
Mar 19, 2013·International Journal of Pharmaceutics·Flore DepreterKarim Amighi
Feb 7, 2015·International Journal of Pharmaceutics·S FranzèF Cilurzo
Jul 2, 2016·Pharmaceuticals·Ana Rita NevesMadalena Pinto
Apr 19, 2017·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Ayca Yildiz-Pekoz, Yildiz Ozsoy
Jul 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fahad AkhtarShuying He

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