Gao Jingjing, Xia Ziting, Vohidova Dilrasbonu, Joseph John, Luo James N, Joshi Nitin
Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Harvard Medical School, Boston, MA 02115, USA.
Acta Pharm Sin B. 2023 Apr;13(4):1400-1428. doi: 10.1016/j.apsb.2022.07.010. Epub 2022 Jul 19.
Emerging therapies based on localized delivery of siRNA to lungs have opened up exciting possibilities for treatment of different lung diseases. Localized delivery of siRNA to lungs has shown to result in severalfold higher lung accumulation than systemic route, while minimizing non-specific distribution in other organs. However, to date, only 2 clinical trials have explored localized delivery of siRNA for pulmonary diseases. Here we systematically reviewed recent advances in the field of pulmonary delivery of siRNA using non-viral approaches. We firstly introduce the routes of local administration and analyze the anatomical and physiological barriers towards effective local delivery of siRNA in lungs. We then discuss current progress in pulmonary delivery of siRNA for respiratory tract infections, chronic obstructive pulmonary diseases, acute lung injury, and lung cancer, list outstanding questions, and highlight directions for future research. We expect this review to provide a comprehensive understanding of current advances in pulmonary delivery of siRNA.
基于将小干扰RNA（siRNA）局部递送至肺部的新兴疗法，为不同肺部疾病的治疗开辟了令人兴奋的可能性。已表明将siRNA局部递送至肺部会导致肺部蓄积比全身给药途径高出数倍，同时将在其他器官中的非特异性分布降至最低。然而，迄今为止，仅有2项临床试验探索了将siRNA局部递送至肺部治疗肺部疾病。在此，我们系统地综述了使用非病毒方法进行肺部siRNA递送领域的最新进展。我们首先介绍局部给药途径，并分析影响siRNA在肺部有效局部递送的解剖学和生理学屏障。然后，我们讨论了用于呼吸道感染、慢性阻塞性肺疾病、急性肺损伤和肺癌的siRNA肺部递送的当前进展，列出未解决的问题，并强调未来研究的方向。我们期望本综述能让读者全面了解siRNA肺部递送的当前进展。
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