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Inhaled extended-release microparticles of heparin elicit improved pulmonary pharmacodynamics against antigen-mediated airway hyper-reactivity and inflammation

Yildiz, Ayca, John, Elinor, Özsoy, Yildiz, Araman, Ahmet, Birchall, James Caradoc, Broadley, Kenneth John and Gumbleton, Mark 2012. Inhaled extended-release microparticles of heparin elicit improved pulmonary pharmacodynamics against antigen-mediated airway hyper-reactivity and inflammation. Journal of Controlled Release 162 (2) , pp. 456-463. 10.1016/j.jconrel.2012.07.008

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Abstract

Inhaled heparin appears to provide benefit in the management of airway hyper-reactivity and inflammation. The pharmacodynamics of inhaled heparin are however transient. Providing sustained heparin concentrations in the respiratory tract should provide for an extended duration of action. We examined the in-vivo efficacy of a nebulised controlled-release microparticle formulation of heparin in modifying antigen-induced airway hyper-reactivity (AHR) and lung inflammation. Heparin-loaded biodegradable poly (d,l-lactide-co-glycolide) microparticles were prepared by spray-drying. Aerosol properties for both nebulised heparin solution and heparin microparticles displayed characteristics consistent with heparin delivery to the respiratory tract. In vitro release assays showed heparin to be released from the microparticles over 8–12 h and for the heparin to remain functional. Temporal pharmacodynamic responses were studied in an ovalbumin-sensitised in vivo model exhibiting AHR and airway inflammation. Despite a reduced total dose of heparin deposited in the airways following nebulisation with heparin microparticles, this treatment led to a more sustained inhibitory effect upon AHR and airway inflammation than equivalent doses of nebulised heparin solution. The work supports extended-release heparin as an inhalation dosing strategy in experimental therapeutic applications aimed at improving the pharmacodynamics of heparin in the treatment of AHR and lung inflammation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Heparin; Airway hyper-reactivity; Lung pharmacodynamics; PLGA microparticles; Asthma; Nebulised aerosol
Publisher: Elsevier
ISSN: 0168-3659
Last Modified: 11 Apr 2019 21:44
URI: http://orca.cf.ac.uk/id/eprint/40661

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