Department of Pharmaceutics and Biopharmacy, Philipps-Universität Marburg, Ketzerbach 63, Marburg, Germany.
Bioconjug Chem. 2012 Jan 18;23(1):3-20. doi: 10.1021/bc200296q. Epub 2011 Nov 1.
Pulmonary delivery provides an easy and well tolerated means of access for the administration of biomacromolecules to the pulmonary epithelium and could therefore be an attractive approach for local and systemic therapies. A growing number of reports, which are summarized in this review, mirror the viability of pulmonary gene delivery. Special attention has been paid to the biological barriers in the lung that must be overcome for successful delivery, and which can be divided into anatomic, physical, immunologic, and metabolic barriers. In light of these barriers, successful nonviral polymer-based formulations of therapeutic genes are presented depending on the chemical nature of the polymer. In addition to polyethyleneimine-based nonviral vectors, which have been most intensively studied for pulmonary gene delivery in the past, other polymeric, dendritic, and targeted materials are also described here, including novel and biodegradable polymers. As new materials need in vitro or ex vivo testing before in vivo application, sophisticated models for all three approaches have been illustrated. Although pulmonary siRNA delivery enjoys popularity in clinical trials, pulmonary gene delivery has so far not been translated into clinical applications. With this review, potential hurdles are demonstrated, but novel approaches that may lead to optimized systems are described as well.
肺部给药为生物大分子向肺部上皮细胞的给药提供了一种简便且可耐受的途径，因此可能成为局部和全身治疗的一种有吸引力的方法。越来越多的报告（本文对此进行了总结）反映了肺部基因传递的可行性。特别关注了肺部中必须克服的生物屏障，这些屏障可以分为解剖屏障、物理屏障、免疫屏障和代谢屏障。根据聚合物的化学性质，本文介绍了成功的基于非病毒聚合物的治疗基因的制剂。除了过去在肺部基因传递中得到最深入研究的基于聚乙烯亚胺的非病毒载体外，本文还描述了其他聚合物、树突状和靶向材料，包括新型和可生物降解的聚合物。由于新材料在体内应用之前需要进行体外或离体测试，因此本文还说明了所有三种方法的复杂模型。尽管肺部 siRNA 传递在临床试验中很受欢迎，但肺部基因传递迄今为止尚未转化为临床应用。通过本文的综述，展示了潜在的障碍，但也描述了可能导致优化系统的新方法。
