Pulmonary delivery of surfactant for treatment of lung diseases

外源性表面活性物质疗法被成功地用于治疗新生儿呼吸窘迫综合征(NRDS)，也可能有益于成人肺部疾病的治疗，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，部分原因是给药时疾病的严重性，以及给药限制，因为目前的标准给药方法是通过气管内滴注生理盐水-表面活性物质混悬液。这种方法也不适合治疗自主呼吸患者，如果早期表面活性物质治疗策略被证明是最佳的，这是一个潜在的要求。通过雾化对表面活性剂悬浮液进行气雾化迄今尚未成功，原因是通过雾化过程使表面活性剂失活，输送效率低，以及由于表面活性剂本身的表面张力较低而存在更多实际困难，如起泡。表面活性物质的粉末雾化吸入可以避免这些问题，并为表面活性物质的输送提供了一种更可行、非侵入性和成本效益高的方法，甚至为其他肺部靶向治疗提供了一种药物输送载体。申请人(朱，一名粉末技术工程师)开发了一种用于将药物输送到肺部的新型干粉吸入技术，拥有几项已获授权和正在申请的专利。拟议的研究旨在将这项技术扩展到肺表面活性物质的输送，因为它能够雾化包括肺表面活性物质在内的少量可呼吸干粉，共同申请人为此进行了广泛的研究(刘易斯，呼吸科医生)。目前的联合项目的总体目标是创造一种满足表面活性物质输送临床要求的新装置。本研究方案的具体目标是改进现有的表面活性物质雾化吸入技术，首先在体外评价雾化表面活性物质的功能完整性和有效性，然后使用小动物模型进行体内评价。

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.