Therapeutic aerosol bioengineering of siRNA for the treatment of inflammatory lung disease by TNFα gene silencing in macrophages.

The development of small interfering RNA (siRNA) to silence specific genes offers a new means of understanding and treating a range of respiratory diseases, including inflammatory lung disease. The alveolar macrophage (AM) is a key component of the inflammatory process in the lungs, associated with high levels of gene expression in inflammatory lung disease and therefore an attractive target for therapeutic siRNA. Delivery of siRNA to macrophages presents a significant delivery challenge, as fully differentiated alveolar macrophages are difficult to access and transfect. In this study we engineered particles suitable for inhalation that would efficiently transfect macrophages postinhalation. The process for encapsulation of siRNA in poly(lactic-co-glycolic acid) microparticles (MPs) was optimized using a double emulsion technique, and the resulting particles were characterized for size, shape, aerosol characteristics, encapsulation efficiency, and integrity of encapsulated siRNA. The cell uptake of the si...