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Inhaled Heparin: Therapeutic Efficacy and Recent Formulations.

Heparin is well known for its anticoagulant and anti-inflammatory properties. Inhaled heparin regimens are increasingly being used to manage lung disease. It has been used to treat cystic fibrosis, thromboembolism, and pulmonary fibrosis, as well as bronchial asthma and asthma-induced airway hypersensitivity. Several preclinical studies attained some useful effects of heparin-administered, parenterally and through inhalation, treatment of lung disease. Besides, recent clinical trials suggest that inhaled heparin for lung diseases is beneficial and safe, but such data remain to be limited. In 2005, the orphan designation was granted by the European Commission for heparin sodium (inhalation use) for the treatment of cystic fibrosis. The positive results of heparin in the pulmonary route necessitate a focus on the preparation and evaluation of heparin in advanced drug delivery systems, namely nano/microparticles and liposomes. Through this pulmonary delivery, heparin is protected from enzymatic degradation within the airway. Heparin is thus passively targeted into the lungs, and long-lasting localized treatment is achieved. On the other hand, these systems have encountered several problems as follows: (1) polymers, such as poly-L-lactide-glycolic acid, poly (lactic acid), and chitosan, used to prepare heparin-loaded microparticle/nanoparticle (MP/NP) systems have not been granted approval for lung application by the FDA and (2) liposomal and NP formulation stability is the main problem of formulation design. We propose that additional in vitro and in vivo research is necessary to assess the clinical applicability of this treatment strategy. The present article discusses heparin treatments for lung diseases and the use of heparin and/or heparin-loaded drugs in advanced delivery systems through the pulmonary route.

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