Ramsey Joanne M, Hibbitts Alan, Barlow James, Kelly Ciara, Sivadas Neeraj, Cryan Sally-Ann
Royal College of Surgeons, Dublin 2, Ireland.
Ther Deliv. 2013 Jan;4(1):59-76. doi: 10.4155/tde.12.133.
The emergence of RNAi offers a potentially exciting new therapeutic paradigm for respiratory diseases. However, effective delivery remains a key requirement for their translation into the clinic and has been a major factor in the limited clinical success seen to date. Inhalation offers tissue-specific targeting of the RNAi to treat respiratory diseases and a diminished risk of off-target effects. In order to deliver RNAi directly to the respiratory tract via inhalation, 'smart' non-viral carriers are required to protect the RNAi during delivery/aerosolization and enhance cell-specific uptake to target cells. Here, we review the state-of-the-art in therapeutic aerosol bioengineering, and specifically non-viral siRNA delivery platforms, for delivery via inhalation. This includes developments in inhaler device engineering and particle engineering, including manufacturing methods and excipients used in therapeutic aerosol bioengineering that underpin the development of smart, cell type-specific delivery systems to target siRNA to respiratory epithelial cells and/or alveolar macrophages.
RNA干扰的出现为呼吸系统疾病提供了一种可能令人兴奋的新治疗模式。然而，有效的递送仍然是将其转化为临床应用的关键要求，并且是迄今为止临床成功有限的一个主要因素。吸入给药可实现RNA干扰对呼吸系统疾病的组织特异性靶向作用，并降低脱靶效应的风险。为了通过吸入将RNA干扰直接递送至呼吸道，需要“智能”非病毒载体在递送/雾化过程中保护RNA干扰，并增强对靶细胞的细胞特异性摄取。在此，我们综述了用于吸入递送的治疗性气溶胶生物工程，特别是非病毒小干扰RNA递送平台的最新进展。这包括吸入器装置工程和颗粒工程的发展，包括治疗性气溶胶生物工程中使用的制造方法和辅料，这些是开发将小干扰RNA靶向呼吸道上皮细胞和/或肺泡巨噬细胞的智能、细胞类型特异性递送系统的基础。
