Pulmonary delivery of surfactant for treatment of lung diseases

外源性表面活性剂治疗已成功用于治疗新生儿呼吸窘迫综合征（NRDS），也可能有益于治疗成人肺部疾病，如急性呼吸窘迫综合征（ARDS）和哮喘。然而，后一种情况下的临床试验结果令人失望，部分原因是在给药时疾病的严重程度，以及给药限制，因为目前的标准给药方法是气管内注射盐表面活性剂悬浮液。该方法也不适合治疗自发呼吸的患者，如果早期的表面活性剂治疗策略被证明是最佳的，则可能需要这种方法。由于表面活性剂在雾化过程中失活，输送效率较低，以及表面活性剂本身表面张力较低而产生泡沫等实际困难，表面活性剂悬浮液的雾化迄今尚未成功。Dr>粉末气溶胶表面活性剂的递送可以避免这些问题，并提供了一个更可行的，非侵入性和成本效益的表面活性剂递送方法，甚至作为其他肺靶向治疗的药物递送载体。申请人（朱，粉末技术工程师）开发了一种新型的干粉吸入技术，用于将药物输送到肺部，拥有多项已授权和正在申请的专利。拟议的研究旨在将该技术扩展到肺表面活性物质的输送，因为它能够雾化少量包括肺表面活性物质在内的可吸入干粉，共同申请人已经对此进行了广泛的研究（Lewis，呼吸病学家）。目前联合项目的总体目标是创造一种满足表面活性剂输送临床要求的新设备。本研究方案的具体目标是改进现有的表面活性剂吸入器技术，先在体外，再在体内用小动物模型评估雾化表面活性剂的功能完整性和功效。

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.