Pulmonary delivery of surfactant for treatment of lung diseases

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Exogenous surfactant therapy is successfully used to treat neonatal respiratory distress syndrome (NRDS) and may also be beneficial in the treatment of adult lung diseases such as acute respiratory distress syndrome (ARDS) and asthma. However, results of clinical trials in the latter setting have been disappointing, in part because of the severity of the disease at the time of administration, as well as delivery limitations, as the curreni standard deliver method is by bolus instillation of a saline-surfactant suspension intratracheally. The method is also not suitable for treatment of spontaneously breathing patients, a potential requirement if earlier surfactant treatment strategies proves optimal. Aerosolization of surfactant suspensions via nebulization has not been successful to date due to inactivation of the surfactant via the nebulization process, poor efficiency of delivery as well as more practical difficulties such as foaming due to the low surface tension of the surfactant itself. Dr> powder aerosol delivery of surfactant could avoid these problems, and provide a more feasible, non-invasive and cost-effective method for surfactant delivery and even as a drug delivery vehicle for other lung-targeted therapies. The applicant (Zhu, a powder technology engineer) has developed a novel dry powder inhalation technology for the delivery of medications to the lung, with several granted and pending patents. The proposed research aims at extending this technology to the delivery of lung surfactant, as it is capable of aerosolizing small quantities of respirable dry powder including lung surfactant, for which the co-applicant has done extensive research (Lewis, respirologist). The overall objective the current joint project is to create a new device which meets the clinical requirements for surfactant delivery. The specific objectives of this research proposal are to modify the existing inhaler technology for surfactant delivery, to evaluate the functional integrity and the efficacy of the aerosolized surfactant in-vitro first and then in vivo using a small animal model.