Pulmonary delivery of surfactant for treatment of lung diseases

外源性表面活性物质治疗成功地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，在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程度以及递送限制，因为目前的标准递送方法是通过静脉内推注盐水-表面活性剂悬浮液。该方法也不适用于自主呼吸患者的治疗，如果早期表面活性剂治疗策略被证明是最佳的，则这是一种潜在的要求。迄今为止，通过雾化的表面活性剂悬浮液的雾化尚未成功，这是由于通过雾化过程的表面活性剂的失活、差的递送效率以及更实际的困难，例如由于表面活性剂本身的低表面张力而产生的发泡。表面活性剂的粉末气雾剂递送可以避免这些问题，并且为表面活性剂递送提供更可行的、非侵入性的和成本有效的方法，甚至作为其他肺靶向治疗的药物递送载体。 申请人（Zhu，粉末技术工程师）开发了一种新型干粉吸入技术，用于将药物输送到肺部，并拥有多项已批准和待批准的专利。拟议的研究旨在将该技术扩展到肺表面活性物质的递送，因为它能够雾化少量可吸入干粉，包括肺表面活性物质，共同申请人对此进行了广泛的研究（刘易斯，呼吸科医生）。当前联合项目的总体目标是创建一种满足表面活性剂输送临床要求的新器械。本研究提案的具体目标是修改现有的表面活性剂递送吸入器技术，首先在体外评价雾化表面活性剂的功能完整性和功效，然后使用小动物模型在体内评价。

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.